Colorectal Cancers

Overview

About 75% of patients with colorectal (CRC) have sporadic (not inherited) disease. The majority involve somatic mutations which result in chromosomal instability (CIN), whilst around a quarter have patterns of gene hypermethylation known as an CpG island methylator phenotype (CIMP), including many with microsatellite instability (MSI). There are a wide variety of genes that are involved in CRC, with tumors having an average of 9 mutated genes.

25% of patients have a family history of CRC. These include a sub-set of patients with defined genetic syndromes (see Predisposing Syndromes, below). The most frequent of these is Lynch Syndrome (also called Hereditary Non-Polyposis Colorectal Cancer) which accounts for approximately 5-8% of all colorectal cancers, and usually associated with germline mutations in mismatch repair genes including: MSH2, MSH6, MLH1, PMS1 and PMS2. There are a range of other syndromes, including Familial Adenomatous Polyposis (FAP), which is an autosomal dominant disorder causing extensive adenomatous polyps in the colon and early onset colorectal cancer. FAP accounts for about 1% of all colorectal cancers. The disorder is characterised by APC gene mutation. FAP is also assciated with elevated risk of extracolonic tumours.

See also: Colorectal (Bowel) Cancer - clinical resources (28)

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 10 March, 2017 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (499)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

GeneLocationAliasesNotesTopicPapers
APC 5q21-q22 GS, DP2, DP3, BTPS2, DP2.5, PPP1R46 -APC and Colorectal Cancer
2273
KRAS 12p12.1 NS, NS3, CFC2, KRAS1, KRAS2, RASK2, KI-RAS, C-K-RAS, K-RAS2A, K-RAS2B, K-RAS4A, K-RAS4B -KRAS and Colorectal Cancer
1685
MSH2 2p21 FCC1, COCA1, HNPCC, LCFS2, HNPCC1 -MSH2 and Colorectal Cancer
1442
CTNNB1 3p22.1 CTNNB, MRD19, armadillo -CTNNB1 and Colorectal Cancer
1206
BRAF 7q34 NS7, BRAF1, RAFB1, B-RAF1 -BRAF and Colorectal Cancer
1092
MLH1 3p21.3 FCC2, COCA2, HNPCC, hMLH1, HNPCC2 Germline
-MLH1 and Lynch Syndrome
1080
PTGS2 1q25.2-q25.3 COX2, COX-2, PHS-2, PGG/HS, PGHS-2, hCox-2, GRIPGHS -PTGS2 (COX2) and Colorectal Cancer
-COX2 Inhibitors for Colorectal Cancer
-COX2 Polymorphisms and Colorectal Cancer
360
EGFR 7p12 ERBB, HER1, mENA, ERBB1, PIG61, NISBD2 -EGFR and Colorectal Cancer
734
TP53 17p13.1 P53, BCC7, LFS1, TRP53 -TP53 and Colorectal Cancer
639
MSH6 2p16 GTBP, HSAP, p160, GTMBP, HNPCC5 -MSH6 and Colorectal Cancer
499
CDKN2A 9p21.3 ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A, P16-INK4A -CDKN2A and Colorectal Cancer
377
CEACAM5 19q13.2 CEA, CD66e -CEACAM5 and Colorectal Cancer
375
PIK3CA 3q26.3 MCM, CWS5, MCAP, PI3K, CLOVE, MCMTC, p110-alpha -PIK3CA and Colorectal Cancer
296
DCC 18q21.3 CRC18, CRCR1, MRMV1, IGDCC1, NTN1R1 -DCC and Colorectal Cancer
280
MTHFR 1p36.22 -MTHFR mutations and polymorphisms and Colorectal Cancer
259
PPARG 3p25 GLM1, CIMT1, NR1C3, PPARG1, PPARG2, PPARgamma -PPARG and Colorectal Cancer
232
CDKN1A 6p21.2 P21, CIP1, SDI1, WAF1, CAP20, CDKN1, MDA-6, p21CIP1 Prognostic
-CDKN1A Expression in Colorectal Cancer
228
MUTYH 1p34.1 MYH -MUTYH and Colorectal Cancer
191
SMAD4 18q21.1 JIP, DPC4, MADH4, MYHRS -SMAD4 and Colorectal Cancer
189
MYC 8q24.21 MRTL, MYCC, c-Myc, bHLHe39 -MYC and Colorectal Cancer
170
BRCA1 17q21.31 IRIS, PSCP, BRCAI, BRCC1, FANCS, PNCA4, RNF53, BROVCA1, PPP1R53 -BRCA1 germliine mutation and increased risk of Colorectal Cancer?
153
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Colorectal Cancer
151
TCF4 18q21.1 E2-2, ITF2, PTHS, SEF2, ITF-2, SEF-2, TCF-4, SEF2-1, SEF2-1A, SEF2-1B, SEF2-1D, bHLHb19 -TCF4 and Colorectal Cancer
147
BAX 19q13.33 BCL2L4 -BAX and Colonic Neoplasms
139
TGFBR2 3p22 AAT3, FAA3, LDS2, MFS2, RIIC, LDS1B, LDS2B, TAAD2, TGFR-2, TGFbeta-RII -TGFBR2 and Colorectal Cancer
136
NRAS 1p13.2 NS6, CMNS, NCMS, ALPS4, N-ras, NRAS1 -NRAS and Colorectal Cancer
121
UGT1A1 2q37 GNT1, UGT1, UDPGT, UGT1A, HUG-BR1, BILIQTL1, UDPGT 1-1 -UGT1A1 and Colorectal Cancer
117
VEGFA 6p12 VPF, VEGF, MVCD1 -VEGFA and Colorectal Cancer
116
PCNA 20pter-p12 ATLD2 -PCNA and Colorectal Cancer
115
NODAL 10q22.1 HTX5 -NODAL and Colorectal Cancer
113
IGF2 11p15.5 GRDF, IGF-II, PP9974, C11orf43 -IGF2 and Colorectal Cancer
112
CDX2 13q12.3 CDX3, CDX-3, CDX2/AS -CDX2 and Colorectal Cancer
102
TCF7L2 10q25.3 TCF4, TCF-4 -TCF7L2 and Colorectal Cancer
97
NAT2 8p22 AAC2, PNAT, NAT-2 -NAT2 and Colorectal Cancer
97
GSTT1 22q11.23 -GSTT1 and Colorectal Cancer
95
MSH3 5q14.1 DUP, MRP1 -MSH3 and Colorectal Cancer
93
MCC 5q21 MCC1 -MCC and Colorectal Cancer
90
MMP2 16q12.2 CLG4, MONA, CLG4A, MMP-2, TBE-1, MMP-II -MMP2 and Colorectal Cancer
89
MUC2 11p15.5 MLP, SMUC, MUC-2 -MUC2 and Colorectal Cancer
88
XRCC1 19q13.2 RCC -XRCC1 and Colorectal Cancer
87
CDH1 16q22.1 UVO, CDHE, ECAD, LCAM, Arc-1, CD324 -CDH1 and Colorectal Cancer
80
MET 7q31 HGFR, AUTS9, RCCP2, c-Met -C-MET and Colorectal Cancer
77
S100A4 1q21 42A, 18A2, CAPL, FSP1, MTS1, P9KA, PEL98 -S100A4 and Colorectal Cancer
-S100A4 and Colorectal Cancer
59
RUNX3 1p36 AML2, CBFA3, PEBP2aC -RUNX3 and Colorectal Cancer
72
MUC1 1q21 EMA, MCD, PEM, PUM, KL-6, MAM6, MCKD, PEMT, CD227, H23AG, MCKD1, MUC-1, ADMCKD, ADMCKD1, CA 15-3, MUC-1/X, MUC1/ZD, MUC-1/SEC Prognostic
-MUC1 and Colorectal Cancer
71
CDKN1B 12p13.1-p12 KIP1, MEN4, CDKN4, MEN1B, P27KIP1 Prognostic
-CDKN1B and Colorectal Cancer
68
MIR21 17q23.1 MIRN21, miR-21, miRNA21, hsa-mir-21 -MicroRNA miR-21 and Colorectal Cancer
67
SMAD2 18q21.1 JV18, MADH2, MADR2, JV18-1, hMAD-2, hSMAD2 -SMAD2 and Colorectal Cancer
64
TGFBR1 9q22 AAT5, ALK5, ESS1, LDS1, MSSE, SKR4, ALK-5, LDS1A, LDS2A, TGFR-1, ACVRLK4, tbetaR-I -TGFBR1 and Colorectal Cancer
63
PMS1 2q31.1 MLH2, PMSL1, hPMS1, HNPCC3 -PMS1 and Colorectal Cancer
60
CHEK2 22q12.1 CDS1, CHK2, LFS2, RAD53, hCds1, HuCds1, PP1425 -CHEK2 and Colorectal Cancer
59
TGFA 2p13 TFGA -TGFA and Colonic Neoplasms
56
ERCC2 19q13.3 EM9, TTD, XPD, TTD1, COFS2, TFIIH -ERCC2 and Colorectal Cancer
53
IGFBP3 7p12.3 IBP3, BP-53 -IGFBP3 and Colorectal Cancer
52
FOS 14q24.3 p55, AP-1, C-FOS -FOS and Colonic Neoplasms
52
ABCC1 16p13.1 MRP, ABCC, GS-X, MRP1, ABC29 -ABCC1 (MRP1) and Colorectal Cancer
50
CACNA1G 17q22 NBR13, Cav3.1, Ca(V)T.1 -CACNA1G and Colorectal Cancer
50
NEUROG1 5q23-q31 AKA, ngn1, Math4C, bHLHa6, NEUROD3 -NEUROG1 and Colorectal Cancer
49
SOCS1 16p13.13 JAB, CIS1, SSI1, TIP3, CISH1, SSI-1, SOCS-1 -SOCS1 and Colorectal Cancer
49
DNMT3B 20q11.2 ICF, ICF1, M.HsaIIIB -DNMT3B and Colorectal Cancer
47
DNMT1 19p13.2 AIM, DNMT, MCMT, CXXC9, HSN1E, ADCADN -DNMT1 and Colorectal Cancer
47
AXIN2 17q24.1 AXIL, ODCRCS -AXIN2 and Colorectal Cancer
46
EPCAM 2p21 ESA, KSA, M4S1, MK-1, DIAR5, EGP-2, EGP40, KS1/4, MIC18, TROP1, EGP314, HNPCC8, TACSTD1 -EPCAM and Colorectal Cancer
46
MMP7 11q22.2 MMP-7, MPSL1, PUMP-1 -MMP7 and Colorectal Cancer
45
BMPR1A 10q22.3 ALK3, SKR5, CD292, ACVRLK3, 10q23del -BMPR1A and Colorectal Cancer
45
NAT1 8p22 AAC1, MNAT, NATI, NAT-1 -NAT1 and Colorectal Cancer
43
LGR5 12q22-q23 FEX, HG38, GPR49, GPR67, GRP49 -LGR5 and Colorectal Cancer
43
TYMS 18p11.32 TS, TMS, HST422 -TYMS and Colorectal Cancer
42
KRT20 17q21.2 K20, CD20, CK20, CK-20, KRT21 -KRT20 and Colorectal Cancer
38
DPYD 1p22 DHP, DPD, DHPDHASE -DPYD and Colorectal Cancer
38
TNFRSF10B 8p22-p21 DR5, CD262, KILLER, TRICK2, TRICKB, ZTNFR9, TRAILR2, TRICK2A, TRICK2B, TRAIL-R2, KILLER/DR5 -TNFRSF10B and Colonic Neoplasms
38
OGG1 3p26.2 HMMH, MUTM, OGH1, HOGG1 -OGG1 and Colorectal Cancer
38
RAC1 7p22 MIG5, Rac-1, TC-25, p21-Rac1 -RAC1 and Colorectal Cancer
38
SFRP1 8p11.21 FRP, FRP1, FrzA, FRP-1, SARP2 -SFRP1 and Colorectal Cancer
38
CRABP1 15q24 RBP5, CRABP, CRABPI, CRABP-I -CRABP1 and Colorectal Cancer
37
TGFB1 19q13.1 CED, LAP, DPD1, TGFB, TGFbeta -TGFB1 and Colorectal Cancer
37
ESR1 6q25.1 ER, ESR, Era, ESRA, ESTRR, NR3A1 -ESR1 and Colorectal Cancer
36
FLT1 13q12 FLT, FLT-1, VEGFR1, VEGFR-1 -FLT1 and Colorectal Cancer
36
NQO1 16q22.1 DTD, QR1, DHQU, DIA4, NMOR1, NMORI -NQO1 and Colorectal Cancer
35
GAPDH 12p13 G3PD, GAPD, HEL-S-162eP -GAPDH and Colorectal Cancer
35
PPARD 6p21.2 FAAR, NUC1, NUCI, NR1C2, NUCII, PPARB -PPAR delta and Colorectal Cancer
35
THBS1 15q15 TSP, THBS, TSP1, TSP-1, THBS-1 -THBS1 and Colorectal Cancer
34
CYP1A2 15q24.1 CP12, P3-450, P450(PA) -CYP1A2 and Colorectal Cancer
34
PTGS1 9q32-q33.3 COX1, COX3, PHS1, PCOX1, PES-1, PGHS1, PTGHS, PGG/HS, PGHS-1 -PTGS1 and Colorectal Cancer
34
MUC5AC 11p15.5 TBM, leB, MUC5, mucin -MUC5AC and Colorectal Cancer
34
XRCC3 14q32.3 CMM6 -XRCC3 and Colorectal Cancer
33
SFRP2 4q31.3 FRP-2, SARP1, SDF-5 -SFRP2 and Colorectal Cancer
33
POLE 12q24.3 FILS, POLE1, CRCS12 -POLE and Colorectal Cancer
32
CHFR 12q24.33 RNF116, RNF196 -CHFR and Colorectal Cancer
31
LOX 5q23.2 -LOX and Colorectal Cancer
30
MLH3 14q24.3 HNPCC7 -MLH3 and Colorectal Cancer
29
EPHX1 1q42.1 MEH, EPHX, EPOX, HYL1 -EPHX1 and Colorectal Cancer
28
EPHB2 1p36.1-p35 DRT, EK5, ERK, CAPB, Hek5, PCBC, EPHT3, Tyro5 -EPHB2 and Colorectal Cancer
28
XIAP Xq25 API3, ILP1, MIHA, XLP2, BIRC4, IAP-3, hIAP3, hIAP-3 -XIAP and Colonic Neoplasms
28
FOXP3 Xp11.23 JM2, AIID, IPEX, PIDX, XPID, DIETER -FOXP3 and Colorectal Cancer
27
IGF1 12q23.2 IGFI, IGF-I, IGF1A -IGF1 and Colorectal Cancer
27
FBXW7 4q31.3 AGO, CDC4, FBW6, FBW7, hAgo, FBX30, FBXW6, SEL10, hCdc4, FBXO30, SEL-10 -FBXW7 and Colorectal Cancer
26
TIMP3 22q12.3 SFD, K222, K222TA2, HSMRK222 -TIMP3 and Colorectal Cancer
26
CYP2C9 10q24 CPC9, CYP2C, CYP2C10, CYPIIC9, P450IIC9 -CYP2C9 and Colorectal Cancer
26
PTP4A3 8q24.3 PRL3, PRL-3, PRL-R -PTP4A3 and Colorectal Cancer
25
HIC1 17p13.3 hic-1, ZBTB29, ZNF901 -HIC1 and Colorectal Cancer
25
ALDH2 12q24.2 ALDM, ALDHI, ALDH-E2 -ALDH2 and Colorectal Cancer
25
RAD50 5q31 NBSLD, RAD502, hRad50 -RAD50 and Colorectal Cancer
24
NOS2 17q11.2 NOS, INOS, NOS2A, HEP-NOS -NOS2 and Colorectal Cancer
24
MRE11 11q21 ATLD, HNGS1, MRE11A, MRE11B -MRE11A and Colorectal Cancer
23
TLR4 9q33.1 TOLL, CD284, TLR-4, ARMD10 -TLR4 and Colorectal Cancer
23
MIR126 9q34.3 MIRN126, mir-126, miRNA126 -MicroRNA mir-126 and Colorectal Cancer
23
BMP4 14q22-q23 ZYME, BMP2B, OFC11, BMP2B1, MCOPS6 -BMP4 and Colorectal Cancer
23
IRS1 2q36 HIRS-1 -IRS1 and Colorectal Cancer
23
CDX1 5q32 -CDX1 and Colorectal Cancer
23
WIF1 12q14.3 WIF-1 -WIF1 and Colorectal Cancer
23
CLDN1 3q28-q29 CLD1, SEMP1, ILVASC -CLDN1 and Colorectal Cancer
23
SEPT9 17q25 MSF, MSF1, NAPB, SINT1, PNUTL4, SeptD1, AF17q25 -SEPT9 and Colorectal Cancer
22
TWIST1 7p21.2 CRS, CSO, SCS, ACS3, CRS1, BPES2, BPES3, TWIST, bHLHa38 -TWIST1 and Colorectal Cancer
22
CHEK1 11q24.2 CHK1 -CHEK1 and Colorectal Cancer
22
EXO1 1q43 HEX1, hExoI -EXO1 and Colorectal Cancer
22
SMO 7q32.3 Gx, SMOH, FZD11 -SMO and Colorectal Cancer
21
LEF1 4q23-q25 LEF-1, TCF10, TCF7L3, TCF1ALPHA -LEF1 and Colonic Neoplasms
21
IL17A 6p12 IL17, CTLA8, IL-17, IL-17A -IL17A and Colorectal Cancer
20
SOX9 17q24.3 CMD1, SRA1, CMPD1, SRXX2, SRXY10 -SOX9 and Colorectal Cancer
20
TIAM1 21q22.11 -TIAM1 and Colorectal Cancer
20
WNT3A 1q42 -WNT3A and Colorectal Cancer
19
CCK 3p22.1 -CCK and Colonic Neoplasms
19
MTRR 5p15.31 MSR, cblE -MTRR and Colorectal Cancer
19
HLTF 3q25.1-q26.1 ZBU1, HLTF1, RNF80, HIP116, SNF2L3, HIP116A, SMARCA3 -HLTF and Colorectal Cancer
19
IL17C 16q24 CX2, IL-17C -IL17C and Colorectal Cancer
19
AREG 4q13.3 AR, SDGF, AREGB, CRDGF -AREG and Colorectal Cancer
19
NOD2 16q21 CD, ACUG, BLAU, IBD1, NLRC2, NOD2B, CARD15, CLR16.3, PSORAS1 -NOD2 and Colorectal Cancer
19
ZEB1 10p11.2 BZP, TCF8, AREB6, FECD6, NIL2A, PPCD3, ZFHEP, ZFHX1A, DELTAEF1 -ZEB1 and Colonic Neoplasms
19
BUB1 2q14 BUB1A, BUB1L, hBUB1 -BUB1 and Colorectal Cancer
18
E2F4 16q22.1 E2F-4 -E2F4 and Colorectal Cancer
18
CLOCK 4q12 KAT13D, bHLHe8 -CLOCK and Colorectal Cancer
18
BMP2 20p12 BDA2, BMP2A -BMP2 and Colorectal Cancer
18
WRN 8p12 RECQ3, RECQL2, RECQL3 -WRN and Colorectal Cancer
17
HFE 6p21.3 HH, HFE1, HLA-H, MVCD7, TFQTL2 -HFE and Colorectal Cancer
17
IRS2 13q34 IRS-2 -IRS2 and Colorectal Cancer
17
MBD4 3q21.3 MED1 -MBD4 and Colorectal Cancer
17
MACC1 7p21.1 7A5, SH3BP4L -MACC1 and Colorectal Cancer
17
BNIP3 10q26.3 NIP3 -BNIP3 and Colorectal Cancer
17
TMEFF2 2q32.3 TR, HPP1, TPEF, TR-2, TENB2, CT120.2 -TMEFF2 and Colorectal Cancer
16
AXIN1 16p13.3 AXIN, PPP1R49 -AXIN1 and Colorectal Cancer
16
CXCL1 4q21 FSP, GRO1, GROa, MGSA, NAP-3, SCYB1, MGSA-a -CXCL1 and Colonic Neoplasms
16
ADIPOQ 3q27 ACDC, ADPN, APM1, APM-1, GBP28, ACRP30, ADIPQTL1 -ADIPOQ and Colorectal Cancer
16
CASR 3q13 CAR, FHH, FIH, HHC, EIG8, HHC1, NSHPT, PCAR1, GPRC2A, HYPOC1 -CASR and Colorectal Cancer
16
FASN 17q25 FAS, OA-519, SDR27X1 -FASN and Colorectal Cancer
16
KLF4 9q31 EZF, GKLF -KLF4 and Colonic Neoplasms
15
ATF3 1q32.3 -ATF3 and Colorectal Cancer
15
PAK1 11q13.5-q14.1 PAKalpha -PAK1 and Colorectal Cancer
15
FCGR3A 1q23 CD16, FCG3, CD16A, FCGR3, IGFR3, IMD20, FCR-10, FCRIII, FCGRIII, FCRIIIA -FCGR3A and Colorectal Cancer
15
CDH13 16q23.3 CDHH, P105 -CDH13 and Colorectal Cancer
15
ALOX15 17p13.3 12-LOX, 15LOX-1, 15-LOX-1 -ALOX15 and Colorectal Cancer
15
NFKB1 4q24 p50, KBF1, p105, EBP-1, NF-kB1, NFKB-p50, NFkappaB, NF-kappaB, NFKB-p105, NF-kappa-B -NFKB1 and Colorectal Cancer
15
GSTA1 6p12.1 GST2, GTH1, GSTA1-1 -GSTA1 and Colorectal Cancer
15
PLAUR 19q13 CD87, UPAR, URKR, U-PAR -PLAUR and Colonic Neoplasms
14
ARHGEF1 19q13.13 LSC, GEF1, LBCL2, SUB1.5, P115-RHOGEF -ARHGEF1 and Colorectal Cancer
14
ALCAM 3q13.1 MEMD, CD166 -ALCAM and Colorectal Cancer
14
BAG1 9p12 HAP, BAG-1, RAP46 Overexpression
Prognostic
-BAG1 overexpression in Colorectal Cancer
14
GREM1 15q13.3 DRM, HMPS, MPSH, PIG2, CRAC1, CRCS4, DAND2, HMPS1, IHG-2, DUP15q, C15DUPq, GREMLIN, CKTSF1B1 -GREM1 and Colorectal Cancer
14
PHIP 6q14 ndrp, BRWD2, WDR11, DCAF14 -PHIP and Colonic Neoplasms
14
IGFBP7 4q12 AGM, PSF, TAF, FSTL2, IBP-7, MAC25, IGFBP-7, RAMSVPS, IGFBP-7v, IGFBPRP1 -IGFBP7 and Colorectal Cancer
14
APOE 19q13.2 AD2, LPG, APO-E, LDLCQ5 -APOE and Colorectal Cancer
14
ESR2 14q23.2 Erb, ESRB, ESTRB, NR3A2, ER-BETA, ESR-BETA -ESR2 and Colorectal Cancer
13
YES1 18p11.31-p11.21 Yes, c-yes, HsT441, P61-YES -Proto-Oncogene Proteins c-yes and Colonic Neoplasms
13
CCNA2 4q27 CCN1, CCNA -CCNA2 and Colorectal Cancer
13
EREG 4q13.3 ER, Ep, EPR -EREG and Colorectal Cancer
13
HMGB1 13q12 HMG1, HMG3, SBP-1 -HMGB1 and Colorectal Cancer
13
CXCL2 4q21 GRO2, GROb, MIP2, MIP2A, SCYB2, MGSA-b, MIP-2a, CINC-2a -CXCL2 and Colorectal Cancer
13
MED1 17q12 PBP, CRSP1, RB18A, TRIP2, PPARBP, CRSP200, DRIP205, DRIP230, PPARGBP, TRAP220 -MED1 and Colorectal Cancer
13
REG4 1p13.1-p12 GISP, RELP, REG-IV -REG4 and Colorectal Cancer
13
TAP1 6p21.3 APT1, PSF1, ABC17, ABCB2, PSF-1, RING4, TAP1N, D6S114E, TAP1*0102N -TAP1 and Colorectal Cancer
13
GDF15 19p13.11 PDF, MIC1, PLAB, MIC-1, NAG-1, PTGFB, GDF-15 -GDF15 and Colorectal Cancer
13
ADH1B 4q23 ADH2, HEL-S-117 -ADH1B and Colorectal Cancer
12
PLA2G2A 1p35 MOM1, PLA2, PLA2B, PLA2L, PLA2S, PLAS1, sPLA2 -PLA2G2A and Colorectal Cancer
12
VIP 6q25 PHM27 -VIP and Colorectal Cancer
12
CTNNA1 5q31.2 CAP102 -CTNNA1 and Colonic Neoplasms
12
LGALS1 22q13.1 GBP, GAL1 -LGALS1 and Colorectal Cancer
12
DKK1 10q11.2 SK, DKK-1 -DKK1 and Colonic Neoplasms
12
B2M 15q21.1 -B2M and Colorectal Cancer
12
KLF5 13q22.1 CKLF, IKLF, BTEB2 -KLF5 and Colorectal Cancer
12
PRINS 10p12.1 NCRNA00074 -PRINS and Colorectal Cancer
12
CRP 1q23.2 PTX1 -CRP and Colorectal Cancer
11
TNFRSF10A 8p21 DR4, APO2, CD261, TRAILR1, TRAILR-1 -TNFRSF10A and Colorectal Cancer
11
WNT2 7q31.2 IRP, INT1L1 -WNT2 and Colorectal Cancer
11
RASSF2 20p13 CENP-34, RASFADIN -RASSF2 and Colorectal Cancer
11
TCF3 19p13.3 E2A, E47, ITF1, VDIR, TCF-3, bHLHb21 -TCF3 and Colorectal Cancer
11
PTPRJ 11p11.2 DEP1, SCC1, CD148, HPTPeta, R-PTP-ETA -PTPRJ and Colorectal Cancer
11
IL4 5q31.1 BSF1, IL-4, BCGF1, BSF-1, BCGF-1 -IL4 and Colorectal Cancer
11
PTPN13 4q21.3 PNP1, FAP-1, PTP1E, PTPL1, PTPLE, PTP-BL, hPTP1E, PTP-BAS -PTPN13 and Colorectal Cancer
11
VIM 10p13 HEL113, CTRCT30 -VIM and Colorectal Cancer
10
TACSTD2 1p32 EGP1, GP50, M1S1, EGP-1, TROP2, GA7331, GA733-1 -TACSTD2 and Colorectal Cancer
10
CEACAM1 19q13.2 BGP, BGP1, BGPI -CEACAM1 and Colorectal Cancer
10
ABCC2 10q24 DJS, MRP2, cMRP, ABC30, CMOAT -ABCC2 and Colorectal Cancer
10
PTPRQ 12q21.2 DFNB84, DFNB84A, PTPGMC1, R-PTP-Q -PTPRQ and Colorectal Cancer
10
FPGS 9q34.1 -FPGS and Colorectal Cancer
10
TAP2 6p21.3 APT2, PSF2, ABC18, ABCB3, PSF-2, RING11, D6S217E -TAP2 and Colorectal Cancer
10
XRCC2 7q36.1 -XRCC2 and Colorectal Cancer
10
APAF1 12q23 CED4, APAF-1 -APAF1 and Colorectal Cancer
10
XAF1 17p13.1 BIRC4BP, XIAPAF1, HSXIAPAF1 -XAF1 and Colonic Neoplasms
10
CYP24A1 20q13 CP24, HCAI, CYP24, P450-CC24 -CYP24A1 and Colonic Neoplasms
10
FOSL1 11q13.1 FRA, FRA1, fra-1 -FOSL1 and Colon Cancer
10
TOP1 20q12-q13.1 TOPI -TOP1 and Colonic Neoplasms
10
TLR2 4q32 TIL4, CD282 -TLR2 and Colorectal Cancer
9
INSR 19p13.3-p13.2 HHF5, CD220 -INSR and Colorectal Cancer
9
EPHB4 7q22 HTK, MYK1, TYRO11 -EPHB4 and Colorectal Cancer
9
POLD1 19q13.3 CDC2, MDPL, POLD, CRCS10 -POLD1 and Colorectal Cancer
9
TAGLN 11q23.3 SM22, SMCC, TAGLN1, WS3-10 -TAGLN and Colorectal Cancer
9
BCL9 1q21 LGS -BCL9 and Colorectal Cancer
9
MYOD1 11p15.1 PUM, MYF3, MYOD, bHLHc1 -MYOD1 and Colorectal Cancer
9
SFRP4 7p14.1 FRP-4, FRPHE, sFRP-4 -SFRP4 and Colorectal Cancer
9
WNT5A 3p21-p14 hWNT5A -WNT5A and Colonic Neoplasms
9
REG1A 2p12 P19, PSP, PTP, REG, ICRF, PSPS, PSPS1 -REG1A and Colorectal Cancer
9
FEN1 11q12.2 MF1, RAD2, FEN-1 -FEN1 and Colorectal Cancer
9
PRDM2 1p36.21 RIZ, KMT8, RIZ1, RIZ2, MTB-ZF, HUMHOXY1 -PRDM2 and Colorectal Cancer
9
SLCO1B1 12p LST1, HBLRR, LST-1, OATP2, OATPC, OATP-C, OATP1B1, SLC21A6 -SLCO1B1 and Colorectal Cancer
9
ALOX5 10q11.2 5-LO, 5LPG, LOG5, 5-LOX -ALOX5 and Colorectal Cancer
8
TCF7 5q31.1 TCF-1 -TCF7 and Colorectal Cancer
8
AKAP12 6q24-q25 SSeCKS, AKAP250 -AKAP12 and Colorectal Cancer
8
TFPI2 7q22 PP5, REF1, TFPI-2 -TFPI2 and Colorectal Cancer
8
PER2 2q37.3 FASPS, FASPS1 -PER2 and Colorectal Cancer
8
PTGER2 14q22 EP2 -PTGER2 and Colorectal Cancer
8
PLA2G4A 1q25 PLA2G4, cPLA2-alpha -PLA2G4A and Colorectal Cancer
8
SFRP5 10q24.1 SARP3 -SFRP5 and Colonic Neoplasms
8
KRT7 12q13.13 K7, CK7, SCL, K2C7 -KRT7 and Colorectal Cancer
8
CFTR 7q31.2 CF, MRP7, ABC35, ABCC7, CFTR/MRP, TNR-CFTR, dJ760C5.1 -CFTR and Colonic Neoplasms
8
DUSP4 8p12-p11 TYP, HVH2, MKP2, MKP-2 -DUSP4 and Colorectal Cancer
8
HPGD 4q34-q35 PGDH, PGDH1, PHOAR1, 15-PGDH, SDR36C1 -HPGD and Colorectal Cancer
8
ZNF217 20q13.2 ZABC1 -ZNF217 and Colorectal Cancer
8
ADIPOR1 1q32.1 CGI45, PAQR1, ACDCR1, CGI-45, TESBP1A -ADIPOR1 and Colorectal Cancer
8
CYP2A6 19q13.2 CPA6, CYP2A, CYP2A3, P450PB, CYPIIA6, P450C2A -CYP2A6 and Colorectal Cancer
8
FZD7 2q33 FzE3 -FZD7 and Colorectal Cancer
8
VCAN 5q14.3 WGN, ERVR, GHAP, PG-M, WGN1, CSPG2 -VCAN and Colorectal Cancer
8
UCHL1 4p14 NDGOA, PARK5, PGP95, PGP9.5, Uch-L1, HEL-117, PGP 9.5 -UCHL1 and Colorectal Cancer
8
CCL20 2q36.3 CKb4, LARC, ST38, MIP3A, Exodus, MIP-3a, SCYA20, MIP-3-alpha -CCL20 and Colorectal Cancer
8
CHIA 1p13.2 CHIT2, AMCASE, TSA1902 -CHIA and Colorectal Cancer
8
CXCR2 2q35 CD182, IL8R2, IL8RA, IL8RB, CMKAR2, CDw128b -CXCR2 and Colonic Neoplasms
8
GLI3 7p13 PHS, ACLS, GCPS, PAPA, PAPB, PAP-A, PAPA1, PPDIV, GLI3FL, GLI3-190 -GLI3 and Colorectal Cancer
8
POLB 8p11.2 -POLB and Colorectal Cancer
8
RRM2 2p25-p24 R2, RR2, RR2M -RRM2 and Colorectal Cancer
7
CSK 15q24.1 -CSK and Colonic Neoplasms
7
EPHB3 3q27.1 ETK2, HEK2, TYRO6 -EPHB3 and Colorectal Cancer
7
NR4A1 12q13 HMR, N10, TR3, NP10, GFRP1, NAK-1, NGFIB, NUR77 -NR4A1 and Colonic Neoplasms
7
SMAD5 5q31 DWFC, JV5-1, MADH5 -SMAD5 and Colorectal Cancer
7
ATOH1 4q22 ATH1, HATH1, MATH-1, bHLHa14 -ATOH1 and Colonic Neoplasms
7
ADH1C 4q23 ADH3 -ADH1C and Colorectal Cancer
7
FSCN1 7p22 HSN, SNL, p55, FAN1 -FSCN1 and Colorectal Cancer
7
IL23R 1p31.3 -IL23R and Colorectal Cancer
7
OLFM4 13q14.3 GC1, OLM4, OlfD, GW112, hGC-1, hOLfD, UNQ362, bA209J19.1 -OLFM4 and Colorectal Cancer
7
NDRG1 8q24.3 GC4, RTP, DRG1, NDR1, NMSL, TDD5, CAP43, CMT4D, DRG-1, HMSNL, RIT42, TARG1, PROXY1 -NDRG1 and Colorectal Cancer
7
ERCC6 10q11.23 CSB, CKN2, COFS, ARMD5, COFS1, RAD26, UVSS1 -ERCC6 and Colorectal Cancer
7
TNFSF13 17p13.1 APRIL, CD256, TALL2, ZTNF2, TALL-2, TRDL-1, UNQ383/PRO715 -TNFSF13 and Colorectal Cancer
7
STAT6 12q13 STAT6B, STAT6C, D12S1644, IL-4-STAT -STAT6 and Colonic Neoplasms
7
FCGR2A 1q23 CD32, FCG2, FcGR, CD32A, CDw32, FCGR2, IGFR2, FCGR2A1 -FCGR2A and Colorectal Cancer
7
PTPRH 19q13.4 SAP1, R-PTP-H -PTPRH and Colorectal Cancer
7
BLM 15q26.1 BS, RECQ2, RECQL2, RECQL3 -BLM and Colorectal Cancer
7
PEBP1 12q24.23 PBP, HCNP, PEBP, RKIP, HCNPpp, PEBP-1, HEL-210, HEL-S-34 -PEBP1 and Colorectal Cancer
7
CEACAM6 19q13.2 NCA, CEAL, CD66c -CEACAM6 and Colorectal Cancer
7
ATG5 6q21 ASP, APG5, APG5L, hAPG5, APG5-LIKE -ATG5 and Colorectal Cancer
7
LAMC2 1q25-q31 B2T, CSF, EBR2, BM600, EBR2A, LAMB2T, LAMNB2 -LAMC2 and Colorectal Cancer
7
NR4A2 2q22-q23 NOT, RNR1, HZF-3, NURR1, TINUR -NR4A2 and Colorectal Cancer
7
SLC5A8 12q23.1 AIT, SMCT, SMCT1 -SLC5A8 and Colonic Neoplasms
7
MTSS1 8p22 MIM, MIMA, MIMB -MTSS1 and Colorectal Cancer
7
MAPK14 6p21.3-p21.2 RK, p38, CSBP, EXIP, Mxi2, CSBP1, CSBP2, CSPB1, PRKM14, PRKM15, SAPK2A, p38ALPHA -MAPK14 and Colonic Neoplasms
6
LTA 6p21.3 LT, TNFB, TNFSF1 -LTA and Colorectal Cancer
6
PTGER4 5p13.1 EP4, EP4R -PTGER4 and Colorectal Cancer
6
AIM2 1q22 PYHIN4 -AIM2 and Colorectal Cancer
6
ARNTL 11p15.3 TIC, JAP3, MOP3, BMAL1, PASD3, BMAL1c, bHLHe5 -ARNTL and Colorectal Cancer
6
SNAI1 20q13.2 SNA, SNAH, SNAIL, SLUGH2, SNAIL1, dJ710H13.1 -SNAI1 and Colonic Neoplasms
6
TJP1 15q13 ZO-1 -TJP1 and Colorectal Cancer
6
CYP27B1 12q14.1 VDR, CP2B, CYP1, PDDR, VDD1, VDDR, VDDRI, CYP27B, P450c1, CYP1alpha -CYP27B1 and Colonic Neoplasms
6
MUC3A 7q22 MUC3, MUC-3A -MUC3A and Colorectal Cancer
6
FRZB 2q32.1 FRE, OS1, FZRB, hFIZ, FRITZ, FRP-3, FRZB1, SFRP3, SRFP3, FRZB-1, FRZB-PEN -FRZB and Colorectal Cancer
6
HDAC3 5q31 HD3, RPD3, RPD3-2 -HDAC3 and Colonic Neoplasms
6
ELAVL1 19p13.2 HUR, Hua, MelG, ELAV1 -ELAVL1 and Colonic Neoplasms
6
POLK 5q13 DINP, POLQ, DINB1 -POLK and Colorectal Cancer
6
MMP12 11q22.2 ME, HME, MME, MMP-12 -MMP12 and Colorectal Cancer
6
PTPRT 20q12-q13 RPTPrho -PTPRT and Colorectal Cancer
6
NDRG2 14q11.2 SYLD -NDRG2 and Colorectal Cancer
6
CSE1L 20q13 CAS, CSE1, XPO2 -CSE1L and Colorectal Cancer
6
MSI1 12q24 -MSI1 and Colorectal Cancer
6
ODC1 2p25 ODC -ODC1 and Colorectal Cancer
6
SLIT2 4p15.2 SLIL3, Slit-2 -SLIT2 and Colorectal Cancer
6
AGR2 7p21.3 AG2, GOB-4, HAG-2, XAG-2, PDIA17, HEL-S-116 -AGR2 and Colorectal Cancer
6
CDH3 16q22.1 CDHP, HJMD, PCAD -CDH3 and Colorectal Cancer
6
GATA4 8p23.1-p22 TOF, ASD2, VSD1, TACHD -GATA4 and Colorectal Cancer
6
GPX2 14q24.1 GPRP, GPx-2, GI-GPx, GPRP-2, GPx-GI, GSHPx-2, GSHPX-GI -GPX2 and Colorectal Cancer
6
MTHFD1 14q24 MTHFC, MTHFD -MTHFD1 and Colorectal Cancer
6
BCL2L2 14q11.2-q12 BCLW, BCL-W, PPP1R51, BCL2-L-2 -BCL2L2 and Colorectal Cancer
6
TDGF1 3p21.31 CR, CRGF, CRIPTO -TDGF1 and Colonic Neoplasms
6
S100P 4p16 MIG9 -S100P and Colonic Neoplasms
6
SLCO1B3 12p12 LST3, HBLRR, LST-2, OATP8, OATP-8, OATP1B3, SLC21A8, LST-3TM13 -SLCO1B3 and Colorectal Cancer
6
KISS1 1q32 HH13, KiSS-1 -KISS1 and Colorectal Cancer
6
RFC1 4p14-p13 A1, RFC, PO-GA, RECC1, MHCBFB, RFC140 -RFC1 and Colorectal Cancer
6
UBE2C 20q13.12 UBCH10, dJ447F3.2 -UBE2C and Colorectal Cancer
5
MAD1L1 7p22 MAD1, PIG9, TP53I9, TXBP181 -MAD1L1 and Colonic Neoplasms
5
ADAMTS1 21q21.2 C3-C5, METH1 -ADAMTS1 and Colorectal Cancer
5
ITGB3 17q21.32 GT, CD61, GP3A, BDPLT2, GPIIIa, BDPLT16 -ITGB3 and Colorectal Cancer
5
CD55 1q32 CR, TC, DAF, CROM -CD55 and Colorectal Cancer
5
MT1G 16q13 MT1, MT1K -MT1G and Colorectal Cancer
5
DMPK 19q13.3 DM, DM1, DMK, MDPK, DM1PK, MT-PK -DMPK and Colorectal Cancer
5
PCDH10 4q28.3 PCDH19, OL-PCDH -PCDH10 and Colorectal Cancer
5
CCL21 9p13 ECL, SLC, CKb9, TCA4, 6Ckine, SCYA21 -CCL21 and Colorectal Cancer
5
ST14 11q24.3 HAI, MTSP1, SNC19, ARCI11, MT-SP1, PRSS14, TADG15, TMPRSS14 -ST14 and Colorectal Cancer
5
SATB1 3p23 -SATB1 and Colorectal Cancer
5
NOX1 Xq22 MOX1, NOH1, NOH-1, GP91-2 -NOX1 and Colonic Neoplasms
5
EPHA7 6q16.1 EHK3, EK11, EHK-3, HEK11 -EPHA7 and Colorectal Cancer
5
LMNA 1q22 FPL, IDC, LFP, CDDC, EMD2, FPLD, HGPS, LDP1, LMN1, LMNC, PRO1, CDCD1, CMD1A, FPLD2, LMNL1, CMT2B1, LGMD1B -LMNA and Colorectal Cancer
5
LGALS4 19q13.2 GAL4, L36LBP -LGALS4 and Colorectal Cancer
5
SLC4A3 2q36 AE3, SLC2C -SLC4A3 and Colonic Neoplasms
5
CASP5 11q22.3 ICH-3, ICEREL-III, ICE(rel)III -CASP5 and Colorectal Cancer
5
PPARGC1A 4p15.1 LEM6, PGC1, PGC1A, PGC-1v, PPARGC1, PGC-1(alpha) -PPARGC1A and Colorectal Cancer
5
ACTB 7p22 BRWS1, PS1TP5BP1 -ACTB and Colorectal Cancer
5
ANGPTL4 19p13.3 NL2, ARP4, FIAF, HARP, PGAR, HFARP, TGQTL, UNQ171, pp1158, ANGPTL2 -ANGPTL4 and Colorectal Cancer
5
PER1 17p13.1 PER, hPER, RIGUI -PER1 and Colorectal Cancer
5
ADIPOR2 12p13.31 PAQR2, ACDCR2 -ADIPOR2 and Colorectal Cancer
5
CD1A 1q23.1 R4, T6, CD1, FCB6, HTA1 -CD1A and Colorectal Cancer
5
HLA-E 6p21.3 MHC, QA1, EA1.2, EA2.1, HLA-6.2 -HLA-E and Colorectal Cancer
5
PLCE1 10q23 PLCE, PPLC, NPHS3 -PLCE1 and Colorectal Cancer
5
CEACAM7 19q13.2 CGM2 -CEACAM7 and Colorectal Cancer
5
NFKBIA 14q13 IKBA, MAD-3, NFKBI -NFKBIA and Colorectal Cancer
4
AKR1B10 7q33 HIS, HSI, ARL1, ARL-1, ALDRLn, AKR1B11, AKR1B12 -AKR1B10 and Colorectal Cancer
4
PGK1 Xq13.3 PGKA, MIG10, HEL-S-68p -PGK1 and Colorectal Cancer
4
LEPR 1p31 OBR, OB-R, CD295, LEP-R, LEPRD -LEPR and Colorectal Cancer
4
KLK6 19q13.3 hK6, Bssp, Klk7, SP59, PRSS9, PRSS18 -KLK6 and Colonic Neoplasms
4
GAB2 11q14.1 -GAB2 and Colorectal Cancer
4
PTPRC 1q31-q32 LCA, LY5, B220, CD45, L-CA, T200, CD45R, GP180 -PTPRC and Colorectal Cancer
4
SEC63 6q21 ERdj2, SEC63L, DNAJC23, PRO2507 -SEC63 and Colorectal Cancer
4
S100A11 1q21 MLN70, S100C, HEL-S-43 -S100A11 and Colorectal Cancer
4
MUC5B 11p15.5 MG1, MUC5, MUC9, MUC-5B -MUC5B and Colonic Neoplasms
4
CDK2AP1 12q24.31 DOC1, ST19, DORC1, doc-1, p12DOC-1 -CDK2AP1 and Colorectal Cancer
4
SMYD3 1q44 KMT3E, ZMYND1, ZNFN3A1, bA74P14.1 -SMYD3 and Colorectal Cancer
4
STC1 8p21.2 STC -STC1 and Colorectal Cancer
4
CSMD1 8p23.2 PPP1R24 -CSMD1 and Colorectal Cancer
4
DRD2 11q23.2 D2R, D2DR -DRD2 and Colorectal Cancer
4
IFITM1 11p15.5 9-27, CD225, IFI17, LEU13, DSPA2a -IFITM1 and Colorectal Cancer
4
TNFRSF10C 8p22-p21 LIT, DCR1, TRID, CD263, TRAILR3, TRAIL-R3, DCR1-TNFR -TNFRSF10C and Colonic Neoplasms
4
ARL11 13q14.2 ARLTS1 -ARL11 and Colorectal Cancer
4
SNRPF 12q23.1 SMF, Sm-F, snRNP-F -SNRPF and Colorectal Cancer
4
TRA 14q11.2 IMD7, TCRA, TCRD, TRA@, TRAC -TRA and Colorectal Cancer
4
EIF3E 8q22-q23 INT6, EIF3S6, EIF3-P48, eIF3-p46 -EIF3E and Colonic Neoplasms
4
CKS2 9q22 CKSHS2 -CKS2 and Colorectal Cancer
4
SACS 13q12 SPAX6, ARSACS, DNAJC29, PPP1R138 -SACS and Colorectal Cancer
4
PER3 1p36.23 GIG13 -PER3 and Colorectal Cancer
4
CD58 1p13 ag3, LFA3, LFA-3 -CD58 and Colonic Neoplasms
4
NRP2 2q33.3 NP2, NPN2, PRO2714, VEGF165R2 -NRP2 and Colorectal Cancer
4
ACTA2 10q23.3 AAT6, ACTSA, MYMY5 -ACTA2 and Colonic Neoplasms
4
MINA 3q11.2 ROX, MDIG, NO52, MINA53 -MINA and Colonic Neoplasms
4
CTBP1 4p16 BARS -CTBP1 and Colonic Neoplasms
4
CRY2 11p11.2 HCRY2, PHLL2 -CRY2 and Colorectal Cancer
4
HSD17B1 17q11-q21 HSD17, EDHB17, EDH17B2, SDR28C1 -HSD17B1 and Colorectal Cancer
4
LOXL2 8p21.3 LOR2, WS9-14 -LOXL2 and Colorectal Cancer
4
CLDN7 17p13.1 CLDN-7, CEPTRL2, CPETRL2, Hs.84359, claudin-1 -CLDN7 and Colorectal Cancer
4
IRF7 11p15.5 IMD39, IRF7A, IRF7B, IRF7C, IRF7H, IRF-7H -IRF7 and Colorectal Cancer
4
HNF4A 20q13.12 TCF, HNF4, MODY, FRTS4, MODY1, NR2A1, TCF14, HNF4a7, HNF4a8, HNF4a9, NR2A21, HNF4alpha -HNF4A and Colonic Neoplasms
4
HHIP 4q28-q32 HIP -HHIP and Colorectal Cancer
4
MIRLET7I 12q14.1 LET7I, let-7i, MIRNLET7I, hsa-let-7i -MicroRNA let-7i and Colorectal Cancer
4
ROBO1 3p12 SAX3, DUTT1 -ROBO1 and Colorectal Cancer
4
PSMD10 Xq22.3 p28, p28(GANK), dJ889N15.2 -PSMD10 and Colorectal Cancer
4
STIM1 11p15.4 GOK, TAM, TAM1, IMD10, STRMK, D11S4896E -STIM1 and Colorectal Cancer
4
WNT11 11q13.5 HWNT11 -WNT11 and Colorectal Cancer
4
SPRY2 13q31.1 hSPRY2 -SPRY2 and Colonic Neoplasms
4
WISP1 8q24.22 CCN4, WISP1c, WISP1i, WISP1tc -WISP1 and Colorectal Cancer
4
CCL19 9p13 ELC, CKb11, MIP3B, MIP-3b, SCYA19 -CCL19 and Colorectal Cancer
4
IL16 15q26.3 LCF, NIL16, PRIL16, prIL-16 -IL16 and Colorectal Cancer
4
GUSB 7q21.11 BG, MPS7 -GUSB and Colorectal Cancer
4
ST7 7q31.2 HELG, RAY1, SEN4, TSG7, ETS7q, FAM4A, FAM4A1 -ST7 and Colorectal Cancer
4
CASP8AP2 6q15 CED-4, FLASH, RIP25 -CASP8AP2 and Colorectal Cancer
4
TOP2A 17q21-q22 TOP2, TP2A -TOP2A Expression in Colorectal Cancer
4
SPHK1 17q25.2 SPHK -SPHK1 and Colonic Neoplasms
4
HAS3 16q22.1 -HAS3 and Colonic Neoplasms
4
INHA 2q35 -INHA and Colorectal Cancer
4
SEPP1 5q31 SeP, SELP, SEPP -SEPP1 and Colorectal Cancer
3
LIG4 13q33-q34 LIG4S -LIG4 and Colorectal Cancer
3
HAS1 19q13.4 HAS -HAS1 and Colonic Neoplasms
3
TXNRD1 12q23-q24.1 TR, TR1, TXNR, TRXR1, GRIM-12 -TXNRD1 and Colorectal Cancer
3
IGF2-AS 11p15.5 PEG8, IGF2AS, IGF2-AS1 -IGF2-AS and Colorectal Cancer
3
CHD5 1p36.31 CHD-5 -CHD5 and Colorectal Cancer
3
APRT 16q24 AMP, APRTD -APRT and Colorectal Cancer
3
DDX5 17q21 p68, HLR1, G17P1, HUMP68 -DDX5 and Colorectal Cancer
3
GATA5 20q13.33 GATAS, bB379O24.1 -GATA5 and Colorectal Cancer
3
INHBA 7p15-p13 EDF, FRP -INHBA and Colorectal Cancer
3
STAT2 12q13.3 P113, ISGF-3, STAT113 -STAT2 and Colonic Neoplasms
3
RBPJ 4p15.2 SUH, csl, AOS3, CBF1, KBF2, RBP-J, RBPJK, IGKJRB, RBPSUH, IGKJRB1 -RBPJ and Colonic Neoplasms
3
ACVR1 2q23-q24 FOP, ALK2, SKR1, TSRI, ACTRI, ACVR1A, ACVRLK2 -ACVR1 and Colonic Neoplasms
3
FOSB 19q13.32 AP-1, G0S3, GOS3, GOSB -FOSB and Colonic Neoplasms
3
MAGEB2 Xp21.3 DAM6, CT3.2, MAGE-XP-2 -MAGEB2 and Colorectal Cancer
3
SPDEF 6p21.3 PDEF, bA375E1.3 -SPDEF and Colonic Neoplasms
3
ING5 2q37.3 p28ING5 -ING5 and Colorectal Cancer
3
DKC1 Xq28 DKC, CBF5, DKCX, NAP57, NOLA4, XAP101 -DKC1 and Colonic Neoplasms
3
KCNQ1OT1 11p15.5 LIT1, Kncq1, KvDMR1, KCNQ10T1, KCNQ1-AS2, KvLQT1-AS, NCRNA00012 -KCNQ1OT1 and Colorectal Cancer
3
BCL2L11 2q13 BAM, BIM, BOD -BCL2L11 and Colorectal Cancer
3
NOTO 2p13.2 -NOTO and Colorectal Cancer
3
APOB 2p24-p23 FLDB, LDLCQ4 -APOB and Colonic Neoplasms
3
FHL2 2q12.2 DRAL, AAG11, FHL-2, SLIM3, SLIM-3 -FHL2 and Colonic Neoplasms
3
BMPR1B 4q22-q24 ALK6, ALK-6, CDw293 -BMPR1B and Colonic Neoplasms
3
HOXD10 2q31.1 HOX4, HOX4D, HOX4E, Hox-4.4 -HOXD10 and Colonic Neoplasms
3
MAX 14q23 bHLHd4 -MAX and Colonic Neoplasms
3
IL12A 3q25.33 P35, CLMF, NFSK, NKSF1, IL-12A -IL12A and Colorectal Cancer
3
VTI1A 10q25.2 MMDS3, MVti1, VTI1RP2, Vti1-rp2 -VTI1A and Colorectal Cancer
3
CRY1 12q23-q24.1 PHLL1 -CRY1 and Colorectal Cancer
3
FER 5q21 TYK3, PPP1R74, p94-Fer -FER and Colonic Neoplasms
3
RANBP2 2q12.3 ANE1, TRP1, TRP2, ADANE, IIAE3, NUP358 -RANBP2 and Colorectal Cancer
3
TNFRSF6B 20q13.3 M68, TR6, DCR3, M68E, DJ583P15.1.1 Amplification
-TNFRSF6B Amplification and Overexpression in Colon Cancer
3
EPAS1 2p21-p16 HLF, MOP2, ECYT4, HIF2A, PASD2, bHLHe73 -EPAS1 and Colorectal Cancer
3
FGF9 13q11-q12 GAF, FGF-9, SYNS3, HBFG-9, HBGF-9 -FGF9 and Colonic Neoplasms
3
MAP3K8 10p11.23 COT, EST, ESTF, TPL2, AURA2, MEKK8, Tpl-2, c-COT -MAP3K8 and Colorectal Cancer
3
WISP3 6q21 PPD, CCN6, LIBC, PPAC, WISP-3 -WISP3 and Colorectal Cancer
3
NNAT 20q11.2-q12 Peg5 -NNAT and Colorectal Cancer
3
EPHA1 7q34 EPH, EPHT, EPHT1 -EPHA1 and Colorectal Cancer
3
SMAD6 15q22.31 AOVD2, MADH6, MADH7, HsT17432 -SMAD6 and Colorectal Cancer
3
KCNQ1 11p15.5-p15.4 LQT, RWS, WRS, LQT1, SQT2, ATFB1, ATFB3, JLNS1, KCNA8, KCNA9, Kv1.9, Kv7.1, KVLQT1 -KCNQ1 and Colorectal Cancer
3
RALGDS 9q34.3 RGF, RGDS, RalGEF -RALGDS and Colorectal Cancer
3
MYCL 1p34.2 LMYC, L-Myc, MYCL1, bHLHe38 -MYCL and Colorectal Cancer
3
PROX1 1q41 -PROX1 and Colonic Neoplasms
3
MVP 16p11.2 LRP, VAULT1 -MVP and Colonic Neoplasms
3
GRASP 12q13.13 TAMALIN -GRASP and Colorectal Cancer
3
CD276 15q23-q24 B7H3, B7-H3, B7RP-2, 4Ig-B7-H3 -CD276 and Colorectal Cancer
3
SEMA3F 3p21.3 SEMA4, SEMAK, SEMA-IV -SEMA3F and Colorectal Cancer
3
PTK7 6p21.1-p12.2 CCK4, CCK-4 -PTK7 and Colonic Neoplasms
3
SNCG 10q23.2-q23.3 SR, BCSG1 -SNCG and Colonic Neoplasms
3
CCR6 6q27 BN-1, DCR2, DRY6, CCR-6, CD196, CKRL3, GPR29, CKR-L3, CMKBR6, GPRCY4, STRL22, CC-CKR-6, C-C CKR-6 -CCR6 and Colorectal Cancer
3
LARS 5q32 LRS, LEUS, LFIS, ILFS1, LARS1, LEURS, PIG44, RNTLS, HSPC192, hr025Cl -LARS and Colorectal Cancer
3
USF1 1q22-q23 UEF, FCHL, MLTF, FCHL1, MLTFI, HYPLIP1, bHLHb11 -USF1 and Colonic Neoplasms
3
NOX4 11q14.3 KOX, KOX-1, RENOX -NOX4 and Colonic Neoplasms
3
TFRC 3q29 T9, TR, TFR, p90, CD71, TFR1, TRFR -TFRC and Colorectal Cancer
3
SAT2 17p13.1 SSAT2 -SAT2 and Colorectal Cancer
3
TSPO 22q13.31 DBI, IBP, MBR, PBR, PBS, BPBS, BZRP, PKBS, PTBR, mDRC, pk18 -TSPO and Colorectal Cancer
3
MBD1 18q21 RFT, PCM1, CXXC3 -MBD1 and Colonic Neoplasms
3
RAD54L 1p32 HR54, hHR54, RAD54A, hRAD54 -RAD54L and Colorectal Cancer
3
BIRC2 11q22.2 API1, MIHB, HIAP2, RNF48, cIAP1, Hiap-2, c-IAP1 -BIRC2 and Colonic Neoplasms
3
IL6R 1q21 IL6Q, gp80, CD126, IL6RA, IL6RQ, IL-6RA, IL-6R-1 -IL6R and Colonic Neoplasms
3
TM4SF1 3q21-q25 L6, H-L6, M3S1, TAAL6 -TM4SF1 and Colorectal Cancer
2
LTBR 12p13 CD18, TNFCR, TNFR3, D12S370, TNFR-RP, TNFRSF3, TNFR2-RP, LT-BETA-R, TNF-R-III -LTBR and Colorectal Cancer
2
MT2A 16q13 MT2 -MT2A and Colonic Neoplasms
2
RASAL1 12q23-q24 RASAL -RASAL1 and Colorectal Cancer
2
ADGRB1 8q24.3 BAI1, GDAIF -BAI1 and Colorectal Cancer
2
AKAP9 7q21-q22 LQT11, PRKA9, AKAP-9, CG-NAP, YOTIAO, AKAP350, AKAP450, PPP1R45, HYPERION, MU-RMS-40.16A -AKAP9 and Colorectal Cancer
2
ATF6 1q23.3 ATF6A -ATF6 and Colonic Neoplasms
2
MS4A1 11q12.2 B1, S7, Bp35, CD20, CVID5, MS4A2, LEU-16 -MS4A1 and Colorectal Cancer
2
MUC7 4q13.3 MG2 -MUC7 and Colorectal Cancer
2
MYH9 22q13.1 MHA, FTNS, EPSTS, BDPLT6, DFNA17, NMMHCA, NMHC-II-A, NMMHC-IIA -MYH9 and Colonic Neoplasms
2
FAT1 4q35 FAT, ME5, CDHF7, CDHR8, hFat1 -FAT1 and Colorectal Cancer
2
BOLL 2q33 BOULE -BOLL and Colonic Neoplasms
2
LASP1 17q11-q21.3 MLN50, Lasp-1 -LASP1 and Colonic Neoplasms
2
MAP2K6 17q24.3 MEK6, MKK6, MAPKK6, PRKMK6, SAPKK3, SAPKK-3 -MAP2K6 and Colonic Neoplasms
2
BCL2L12 19q13.3 -BCL2L12 and Colonic Neoplasms
2
HIP1 7q11.23 SHON, HIP-I, ILWEQ, SHONbeta, SHONgamma -HIP1 and Colonic Neoplasms
2
RALB 2q14.2 -RALB and Colorectal Cancer
2
ATP7A Xq21.1 MK, MNK, DSMAX, SMAX3 -ATP7A and Colonic Neoplasms
2
ADAMTS9 3p14.1 -ADAMTS9 and Colorectal Cancer
2
MIR100 11q24.1 MIRN100, miR-100 -MIR100 and Colonic Neoplasms
2
MTUS1 8p22 ATBP, ATIP, ICIS, MP44, MTSG1 -MTUS1 and Colonic Neoplasms
2
MUC17 7q22.1 MUC3 -MUC17 and Colonic Neoplasms
2
C2orf40 2q12.2 ECRG4 -C2orf40 and Colorectal Cancer
2
TOPBP1 3q22.1 TOP2BP1 -TOPBP1 and Colorectal Cancer
2
PITX1 5q31.1 BFT, CCF, POTX, PTX1, LBNBG -PITX1 and Colorectal Cancer
2
CASP4 11q22.3 TX, Mih1, ICH-2, Mih1/TX, ICEREL-II, ICE(rel)II -CASP4 and Colonic Neoplasms
2
TACR1 2p12 SPR, NK1R, NKIR, TAC1R -TACR1 and Colorectal Cancer
2
ADRM1 20q13.33 ARM1, ARM-1, GP110 -ADRM1 and Colorectal Cancer
2
NAV1 1q32.3 POMFIL3, UNC53H1, STEERIN1 -NAV1 and Colonic Neoplasms
2
ZFP36 19q13.1 TTP, G0S24, GOS24, TIS11, NUP475, zfp-36, RNF162A -ZFP36 and Colonic Neoplasms
2
PRKCDBP 11p15.4 SRBC, HSRBC, CAVIN3, cavin-3 -PRKCDBP and Colorectal Cancer
2
IL12B 5q33.3 CLMF, NKSF, CLMF2, IMD28, IMD29, NKSF2, IL-12B -IL12B and Colorectal Cancer
2
ZNF350 19q13.41 ZFQR, ZBRK1 -ZNF350 and Colonic Neoplasms
2
ADAM29 4q34 CT73, svph1 -ADAM29 and Colorectal Cancer
2
KLK14 19q13.3-q13.4 KLK-L6 -KLK14 and Colonic Neoplasms
2
ARHGEF12 11q23.3 LARG, PRO2792 -ARHGEF12 and Colorectal Cancer
2
PCM1 8p22-p21.3 PTC4, RET/PCM-1 -PCM1 and Colorectal Cancer
2
RRM2B 8q23.1 P53R2, MTDPS8A, MTDPS8B -RRM2B and Colonic Neoplasms
2
ING2 4q35.1 ING1L, p33ING2 -ING2 and Colonic Neoplasms
2
WWTR1 3q23-q24 TAZ -WWTR1 and Colorectal Cancer
2
TPM1 15q22.1 CMH3, TMSA, CMD1Y, LVNC9, C15orf13, HTM-alpha -TPM1 and Colonic Neoplasms
2
SFPQ 1p34.3 PSF, POMP100, PPP1R140 -SFPQ and Colonic Neoplasms
2
GAS7 17p13.1 MLL/GAS7 -GAS7 and Colorectal Cancer
2
RIN1 11q13.2 -RIN1 and Colonic Neoplasms
2
PPP1R3A 7q31.1 GM, PP1G, PPP1R3 -PPP1R3A and Colorectal Cancer
2
SGK1 6q23 SGK -SGK1 and Colonic Neoplasms
2
GJB2 13q11-q12 HID, KID, PPK, CX26, DFNA3, DFNB1, NSRD1, DFNA3A, DFNB1A -GJB2 and Colorectal Cancer
2
MIR106A Xq26.2 mir-106, MIRN106A, mir-106a -MIR106A and Colorectal Cancer
1
ERC1 12p13.3 ELKS, Cast2, ERC-1, RAB6IP2 -ERC1 and Colorectal Cancer
1
PDCD6 5p15.33 ALG2, ALG-2, PEF1B -PDCD6 and Colonic Neoplasms
1
MAFG 17q25.3 hMAF -MAFG and Colonic Neoplasms
1
MIR122 18q21.31 MIR122A, MIRN122, mir-122, MIRN122A, miRNA122, miRNA122A, hsa-mir-122 -MIR122 and Colonic Neoplasms
1
REST 4q12 XBR, NRSF -REST and Colorectal Cancer
1
SETD1B 12q24.31 KMT2G, Set1B -SETD1B and Colorectal Cancer
1
HINT1 5q31.2 HINT, NMAN, PKCI-1, PRKCNH1 -HINT1 and Colonic Neoplasms
1
MIR1226 3p21.31 MIRN1226, mir-1226, hsa-mir-1226 -MicroRNA miR-1226 and Colorectal Cancer
1
ETV3 1q21-q23 PE1, METS, PE-1, bA110J1.4 -ETV3 and Colorectal Cancer
1
RAP2A 13q34 KREV, RAP2, K-REV, RbBP-30 -RAP2A and Colonic Neoplasms
1
NEMF 14q22 NY-CO-1, SDCCAG1 -NEMF and Colonic Neoplasms
1
GOLGA5 14q32.12 RFG5, GOLIM5, ret-II -GOLGA5 and Colorectal Cancer
1
STEAP2 7q21.13 STMP, IPCA1, PUMPCn, STAMP1, PCANAP1 -STEAP2 and Colonic Neoplasms
1
PCDH7 4p15 BHPCDH, BH-Pcdh, PPP1R120 -PCDH7 and Colonic Neoplasms
1
PDCD2 6q27 RP8, ZMYND7 -PDCD2 and Colonic Neoplasms
1
HSP90AA1 14q32.33 EL52, HSPN, LAP2, HSP86, HSPC1, HSPCA, Hsp89, Hsp90, LAP-2, HSP89A, HSP90A, HSP90N, HSPCAL1, HSPCAL4 -HSP90AA1 and Colonic Neoplasms
1
MIR1297 13 MIRN1297, mir-1297, hsa-mir-1297 -MicroRNA miR-1297 and Colorectal Cancer
1
C2orf44 2p23.3 WDCP, PP384 -C2orf44 and Colorectal Cancer
1
CCKBR 11p15.4 GASR, CCK-B, CCK2R -CCKBR and Colonic Neoplasms
SMAD7 18q21.1 CRCS3, MADH7, MADH8 -SMAD7 and Colorectal Cancer
LINC00632 Xq27.1 -RP1-177G6.2 and Colorectal Cancer

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Genetic Syndromes

There are a range of genetic syndromes which predispose to colorectal cancer:

SyndromeMajor gene(s)Notes
Familial Adenomatous Polyposis (FAP)APC
- Attenuated Familial Adenomatous Polyposis (AFAP)APC A variant of FAP characterized by a later age of onset, lower number of polyps compared to FAP, which is defined as > 100 polyps, and more proximal localization of the polyps.
Lynch SyndromeMLH1, MSH2, MSH6 ....Also called: Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
MYH-Associated Polyposis
Familial CRC
PTEN hamartoma tumor syndromesPTEN
- Cowden SyndromePTEN
- Bannayan-Riley-Ruvalcaba Syndrome (BRRS)PTEN
Peutz-Jeghers syndrome (PJS)STK11PJS is an autosomal-dominant condition characterized by the gastrointestinal polyposis, mucocutaneous pigmentation, and predisposition to a range of epithelial cancers: including colorectal, gastric, pancreatic, breast, and ovarian cancers. Women also have increased risk of sex cord tumors with annular tubules.
Juvenile polyposis syndrome (JPS)MADH4, BMPR1A
CHEK2 family cancer syndromeCHEK2Not fully defined
Hereditary mixed polyposis syndrome
Serrated polyposis syndrome

Sources:

Latest Publications

Jauhri M, Bhatnagar A, Gupta S, et al.
Prevalence and coexistence of KRAS, BRAF, PIK3CA, NRAS, TP53, and APC mutations in Indian colorectal cancer patients: Next-generation sequencing-based cohort study.
Tumour Biol. 2017; 39(2):1010428317692265 [PubMed] Related Publications
Colorectal cancer incidences are on a rise in India. In this study, we have analyzed the mutation frequencies of six potential biomarkers, their coexistence, association with clinicopathological characteristics, and tumor location in Indian colorectal cancer patients. Next-generation sequencing was performed to identify mutations in the six potential biomarker genes using formalin-fixed paraffin-embedded tissue blocks of 112 colorectal cancer patients. The mutation frequency observed in KRAS, BRAF, PIK3CA, NRAS, TP53, and APC was 35.7%, 7.1%, 16.1%, 6.3%, 39.3%, and 29.5%, respectively. The significant associations of mutations were KRAS with age less than 60 years (p = 0.041), PIK3CA with males (p = 0.032), tumor stage I-II (p = 0.013), lack of metastasis in lymph nodes (p = 0.040), NRAS with rectum (p = 0.002), and APC with T2 stage of tumor growth (p = 0.013). No single patient harbored mutations in these six genes or any five genes simultaneously. Significance was noted in coexistence of KRAS with APC (p = 0.024) and mutual exclusion of KRAS with BRAF (p = 0.029). PIK3CA exon 9 was observed to be more frequently associated with KRAS mutations than PIK3CA exon 20 (p = 0.072). NRAS mutations were mutually exclusive with BRAF and PIK3CA mutations. As per our knowledge, this is the first next-generation sequencing-based biomarker study in Indian colorectal cancer patients. Frequent coexistence of gene mutations in pairs and triplets suggests that synergistic effect of overlapping mutations might further trigger the disease. In addition, infrequent coexistence of multiple gene mutations hints toward different signaling pathways for colorectal cancer tumorigenesis.

Liu Y, Zuo T, Zhu X, et al.
Differential expression of hENT1 and hENT2 in colon cancer cell lines.
Genet Mol Res. 2017; 16(1) [PubMed] Related Publications
Human equilibrative nucleoside transporters (hENT) 1 and 2, encoded by SLC29A1 and SLC29A2, permit the bidirectional passage of nucleoside analogues into cells and may correlate with clinical responses to chemotherapy in patients with colorectal cancer (CRC). The purpose of this study was to evaluate the expression profiles of SLC29A1 and SLC29A2 in human cancer cell lines. Using quantitative real-time polymerase chain reaction, we comprehensively profiled the transcription levels of SLC29A1 and SLC29A2 in 16 colon cancer cell lines. We validated the ubiquitous and heterogeneous distribution of SLC29A1 and SLC29A2 in human colon cancer cell lines and demonstrated that SLC29A1 was highly expressed in 25% of metastatic cell lines (Colo201 and Colo205) and 62.5% of primary cell lines (Caco2, Colo320, HCT116, RKO, and SW48). For the first time, we showed that both SLC29A1 and SLC29A2 were expressed at lower levels in colon cancer cell lines originating from metastatic sites than from primary sites. These findings indicate that most patients with metastatic CRC (mCRC) may have low hENT1 expression, and treatment with nucleoside analogues may be inefficient. However, some patients still show high hENT1 expression and have a high probability of benefiting from these drugs. Therefore, evaluating transporter expression profiles and different drug responses between primary and metastatic tumors in patients with mCRC is important. Further assessment of the association between hENTs and drug-based treatment of mCRC is required to elucidate the mechanisms of chemotherapy resistance.

Zekri J, Al-Shehri A, Mahrous M, et al.
Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes.
Genet Mol Res. 2017; 16(1) [PubMed] Related Publications
Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors. Most mutations were at codon 12 (89%) and were associated with metastasis [odds ratio (OR) = 1.38 (95%CI = 1.14-1.67] and occurrence of >40 µg/L carcinoembryonic antigen (CEA) [OR = 1.33 (1.1-1.74)] during diagnosis. Patients in stages I-III of the disease with wild-type K-ras tumors had a median relapse free survival (RFS) of 29 months in contrast to 22 months for those with the mutated K-ras tumor (P = 0.0357). In multivariate analysis, only the stage of the disease significantly predicted RFS (P = 0.001). Patients in stage IV of CRC with the wild-type K-ras tumor did not reach the median overall survival (OS), whereas patients with the mutated K-ras tumor survived for 23.5 months (P = 0.044). CEA level >40 µg/L (P = 0.004) and status of K-ras (P = 0.044) were independent predictors of OS. This is the largest study investigating K-ras mutations in patients with CRC in the Middle East. Mutations were associated with advanced stage of CRC, higher serum CEA, shorter RFS and OS.

Ghanbari R, Rezasoltani S, Hashemi J, et al.
Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients.
Arch Iran Med. 2017; 20(2):92-95 [PubMed] Related Publications
BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Early diagnosis of this neoplasm is critical and may reduce patients' mortality. MicroRNAs are small non-coding RNA molecules whose expression pattern can be altered in various diseases such as CRC.
METHODS: In this study, we evaluated the expression levels of miR-142-3p, miR-26a-5p (their reduced expression in plasma samples of CRC patients was previously confirmed), miR-4478 and miR-1295-3p (their reduced expression in stool samples of CRC patients was previously confirmed) in tissue samples of CRC patients in comparison to healthy subjects. To achieve this purpose, total RNA including small RNA was extracted from 53 CRC and 35 normal subjects' Formalin-fixed, Paraffin-embedded (FFPE) tissue samples using the miRNeasy FFPE Mini Kit. The expression levels of these four selected miRNAs were measured using quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR).
RESULTS: We found that the expression levels of miR-4478 and miR-1295b-3p (two previously down-regulated fecal miRNAs) were significantly decreased in FFPE samples of CRC patients compared to healthy controls. On the other hand, no significant differences were seen in expression levels of miR-142-3p and miR-26a-5p (two previously down-regulated circulating miRNAs) in FFPE samples between these two groups.
CONCLUSION: Regarding current findings, it may be concluded that to diagnose CRC patients based on the miRNAs approach, stool samples are more likely preferable to plasma samples; nevertheless, additional studies with more samples are needed to confirm the results.

Iwata N, Ishikawa T, Okazaki S, et al.
Clinical Significance of Methylation and Reduced Expression of the Quaking Gene in Colorectal Cancer.
Anticancer Res. 2017; 37(2):489-498 [PubMed] Related Publications
BACKGROUND: This study investigated abnormal methylation in colorectal cancer (CRC) and the potential role of the Quaking RNA-binding protein (QKI) gene in tumorigenesis.
MATERIALS AND METHODS: Oligonucleotide microarray expression profiling was carried out on a panel of primary CRC specimens (n=17) and CRC cell lines (n=5), followed by methylation analysis using methylation-specific polymerase chain reaction. QKI expression levels were assessed in 156 primary CRCs by qRT-PCR and immunohistochemistry.
RESULTS: Low QKI expression was observed in 47.7% in CRCs. QKI promoter methylation was detected in 32.1% of patients with CRC, and in these patients mRNA expression in tumor tissue was significantly down-regulated compared to matched normal tissues (p=0.049). There was a significant relationship between low QKI expression and recurrence after surgery (p=0.004). Low QKI expression was an independent risk factor for recurrence after surgery in 153 patients with CRC without distant metastases (p=0.036).
CONCLUSION: Patients with tumors expressing low levels of QKI experienced significantly higher rates of tumor recurrence after curative surgery and worse prognoses. Methylation of the QKI promoter and concomitant reduced expression of QKI mRNA may be important for CRC initiation and progression. Loew QKI expression may be a useful clinical biomarker for predicting recurrence and prognosis.

Yang W, Ning N, Jin X
The lncRNA H19 Promotes Cell Proliferation by Competitively Binding to miR-200a and Derepressing β-Catenin Expression in Colorectal Cancer.
Biomed Res Int. 2017; 2017:2767484 [PubMed] Free Access to Full Article Related Publications
H19, a paternally imprinted noncoding RNA, has been found to be overexpressed in various cancers, including colorectal cancer (CRC), and may function as an oncogene. However, the mechanism by which H19 regulates CRC progression remains poorly understood. In this study, we aimed to assess H19 expression levels in CRC tissues, determine the effect of H19 on CRC proliferation, and explore the mechanism by which H19 regulates the proliferation of CRC. We measured H19 expression using qRT-PCR and analysed the effects of H19 on colon cancer cell proliferation via cell growth curve, cell viability assay, and colony formation assays. To elucidate the mechanism underlying these effects, we analysed the interactions between H19 and miRNAs and identified the target gene to which H19 and miRNA competitively bind using a series of molecular biological techniques. H19 expression was upregulated in CRC tissues compared with adjacent noncancerous tissues. H19 overexpression facilitated colon cancer cell proliferation, whereas H19 knockdown inhibited cell proliferation. miR-200a bound to H19 and inhibited its expression, thereby decreasing CRC cell proliferation. β-Catenin was identified as a target gene of miR-200a. H19 regulated β-catenin expression and activity by competitively binding to miR-200a. H19 promotes cell proliferation by competitively binding to miR-200a and derepressing β-catenin in CRC.

Kamal A, Darwish RK, Saad S, et al.
Association of Osteopontin Gene Polymorphisms with Colorectal Cancer.
Cancer Invest. 2017; 35(2):71-77 [PubMed] Related Publications
We investigated the association of the Osteopontin (OPN) (rs9138 and rs1126616) polymorphisms with colorectal cancer (CRC). One hundred CRC patients and 112 healthy individuals were subjected to OPN (rs9138 and rs1126616) genotyping and measurement of OPN protein plasma level. The C allele of OPN rs1126616 and the CC haplotype were significantly higher in CRC patient (p = 0.036, 0.003, respectively). In females, the C allele of OPN rs9318 (A/C) polymorphism was significantly associated with increased CRC risk (p = 0.036). The plasma OPN level >104.35 ng/mL was significantly associated with CRC. Our findings suggest a significant role played by OPN (rs9138 and rs1126616) in colorectal carcinogenesis.

Cicenas J, Tamosaitis L, Kvederaviciute K, et al.
KRAS, NRAS and BRAF mutations in colorectal cancer and melanoma.
Med Oncol. 2017; 34(2):26 [PubMed] Related Publications
Cancers are the group of diseases, which arise because of the uncontrolled behavior of some of the genes in our cells. There are possibilities of gene amplifications, overexpressions, deletions and other anomalies which might lead to the development and spread of cancer. One of the most dangerous ways to the cancers is the mutations of the genes. The mutated genes can start unstoppable proliferation of cells, their uncontrolled motility, protection from apoptosis, the DNA mutation enhancement as well as other anomalies, leading to the cancer. This review focuses on the genes, which are frequently mutated in various cancers and are known to be important in the advance and progression of colorectal cancer and melanoma, namely KRAS, NRAS and BRAF.

Gao XH, Li J, Liu Y, et al.
ZNF148 modulates TOP2A expression and cell proliferation via ceRNA regulatory mechanism in colorectal cancer.
Medicine (Baltimore). 2017; 96(1):e5845 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Competing endogenous RNA (ceRNA) regulation is a novel hypothesized mechanism that states RNA molecules share common target microRNAs (miRNAs) and may competitively combine into the same miRNA pool.
METHODS: Zinc finger protein 148 (ZNF148) and TOP2A expression were analyzed in 742 colorectal cancer (CRC) tissues using immunohistochemistry (IHC). ZNF148 mRNA, TOP2A mRNA, miR101, miR144, miR335, and miR365 expression were estimated in 53 fresh frozen CRC tissues by reverse transcription polymerase chain reaction. Mechanisms underpinning ceRNA were examined using bioinformatics, correlation analysis, RNA interference, gene over-expression, and luciferase assays.
RESULTS: Protein levels of ZNF148 and TOP2A detected by IHC positively correlated (Spearman correlation coefficient [rs] = 0.431, P < 0.001); mRNA levels of ZNF148 and TOP2A also positively correlated (r = 0.591, P < 0.001). Bioinformatics analysis demonstrated that ZNF148 and TOP2A mRNA had 13 common target miRNAs, including miR101, miR144, miR335, and miR365. Correlation analysis demonstrated that levels of ZNF148 mRNA were negatively associated with levels of miR144, miR335, and miR365. Knockdown and overexpression tests showed that ZNF148 mRNA and TOP2A mRNA regulated each other in HCT116 cells, respectively, but not in Dicer-deficient HCT116 cells. Luciferase assays demonstrated that ZNF148 and TOP2A regulated each other through 3'UTR. Overexpression of ZNF148 mRNA and TOP2A mRNA caused significant downregulation of miR101, miR144, miR335, and miR365 in the HCT116 cells. We also found that knockdown of ZNF148 and TOP2A significantly promoted cell growth, and overexpression of ZNF148 and TOP2A inhibited cell proliferation, which was abrogated in Dicer-deficient HCT116 cells.
CONCLUSION: ZNF148 and TOP2A regulate each other through ceRNA regulatory mechanism in CRC, which has biological effects on cell proliferation.

Li X, Zhang G, Wang Y, et al.
Loss of periplakin expression is associated with the tumorigenesis of colorectal carcinoma.
Biomed Pharmacother. 2017; 87:366-374 [PubMed] Related Publications
Periplakin (PPL), a member of the plakin protein family, has been reported to be down-expressed in urothelial carcinoma. The role of PPL in human colorectal cancer, however, remains largely unknown. Also little is known about the contribution of PPL to the malignant property of colorectal cancer and the intracellular function of PPL. In this study, we demonstrated that PPL was apparently down-expressed in colon carcinomas compared with normal and para-carcinoma tissues, which was correlated with the tumor size. Enforced expression of PPL in HT29 cells inhibited its proliferation evidenced by decreased expression of phosphorylated ERK and PCNA. Furthermore, PPL overexpression could reduce metastasis and epithelial-mesenchymal transition (EMT) of HT29 cells, with decreased expression of N-cadherin, Snail, Slug and α-SMA while increased expression of E-cadherin. On the contrary, the PPL knockdown could promote the cell proliferation, migratory, invasive and EMT ability of HT29 cells. Moreover, enforced expression of PPL induced G1/G0 cell cycle arrest, with decreased cyclin D1, p-Rb and increased expression of p27(kib), which could be reversed by PPL knockdown. In addition, PPL overexpression inhibited the growth of colon cancer allograft in vivo. Taken together, acted as a tumor suppressor in colon cancer progression, PPL could be a new biomarker or potential therapeutic target in colon cancer.

Laczmanska I, Skiba P, Karpinski P, et al.
Customized Array Comparative Genomic Hybridization Analysis of 25 Phosphatase-encoding Genes in Colorectal Cancer Tissues.
Cancer Genomics Proteomics. 2017; 14(1):69-74 [PubMed] Free Access to Full Article Related Publications
BACKGROUND/AIM: Molecular mechanisms of alterations in protein tyrosine phosphatases (PTPs) genes in cancer have been previously described and include chromosomal aberrations, gene mutations, and epigenetic silencing. However, little is known about small intragenic gains and losses that may lead to either changes in expression or enzyme activity and even loss of protein function.
MATERIALS AND METHODS: The aim of this study was to investigate 25 phosphatase genes using customized array comparative genomic hybridization in 16 sporadic colorectal cancer tissues.
RESULTS: The analysis revealed two unique small alterations: of 2 kb in PTPN14 intron 1 and of 1 kb in PTPRJ intron 1. We also found gains and losses of whole PTPs gene sequences covered by large chromosome aberrations.
CONCLUSION: In our preliminary studies using high-resolution custom microarray we confirmed that PTPs are frequently subjected to whole-gene rearrangements in colorectal cancer, and we revealed that non-polymorphic intragenic changes are rare.

Santos MD, Silva C, Rocha A, et al.
Prognostic and Therapeutic Potential Implications of Genetic Variability in Prostaglandin E2 Pathway Genes in Rectal Cancer.
Anticancer Res. 2017; 37(1):281-291 [PubMed] Related Publications
AIM: To evaluate the prognostic significance and potential therapeutic implication of genetic variability in prostaglandin E2 pathway genes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery.
MATERIALS AND METHODS: This cohort study included 167 patients with LARC, treated with nCRT followed by surgery. A total of 61 single nucleotide polymorphisms (SNPs) were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard tumor regression grade (TRG). The patients were divided as 'good responders' (Mandard TGR1-2) and 'poor responders' (Mandard TRG3-5). We examined prognostic value of polymorphisms studied to determine if they are related to Mandard response.
RESULTS: Mandard tumor response and rs17268122 in ATP binding cassette subfamily C member (ABCC4) gene were the only two parameters with independent prognostic significance for disease-free survival.
CONCLUSION: tagSNP ABCC4 rs17268122 appears to be a prognostic factor in LARC treated with nCRT and surgery, independently of response to nCRT. The screening of ABCC4 rs17268122 tagSNP and the Mandard tumor response in clinical practice may help to identify patients with different rectal cancer prognosis and contribute to an individualized therapeutic decision tree.

Fujiyoshi K, Yamamoto G, Takenoya T, et al.
Metastatic Pattern of Stage IV Colorectal Cancer with High-Frequency Microsatellite Instability as a Prognostic Factor.
Anticancer Res. 2017; 37(1):239-247 [PubMed] Related Publications
BACKGROUND: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear.
PATIENTS AND METHODS: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Stage IV cases were selected, and clinical and molecular features were evaluated.
RESULTS: There was no significant survival difference observed between MSI-H CRC and microsatellite-stable (MSS) CRC in patients with stage IV disease (3.92 vs. 2.50 years; p=0.766). However, hematogenous and lymphogenous metastasis-dominant CRC with MSI-H demonstrated poor prognosis, whereas peritoneal metastasis-dominant CRC with MSI-H demonstrated good prognosis, (1.33 vs. 5.2 years; p=0.006).
CONCLUSION: Prognosis of stage IV CRC with MSI-H depended on the metastatic pattern. These findings provide useful information for the adaptation of CRC immunotherapy.

Zhou X, Xie S, Yuan C, et al.
Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer.
Cell Physiol Biochem. 2016; 40(6):1433-1442 [PubMed] Related Publications
BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Sprouty proteins are modulators of mitogeninduced signal transduction processes and therefore can influence the process of cancerogenesis. The encoded protein of Sprouty homolog 4 (SPRY4) is associated with various human cancers. However, its biological role and clinical significance in CRC development and progression are unknown.
METHODS: The aim of this study was to evaluate the expression and biological role of SPRY4 in colorectal cancer. qRT-PCR was performed to investigate the expression of SPRY4 in tumor tissues and corresponding non tumor colorectal tissues from 70 patients. The effect of SPRY4 on proliferation was evaluated by MTT and colony formation assays. CRC cells transfected with SPRY4 were injected into nude mice to study the effect of SPRY4 on tumorigenesis in vivo.
RESULTS: The lower expression of SPRY4 was remarkably correlated with deep tumor invasion and advanced TNM stage. Multivariate analyses revealed that SPRY4 expression served as an independent predictor for overall survival. Using 5-aza treatment, we also observed that SPRY4 expression can be affected by DNA methylation. Further experiments revealed that overexpressed SPRY4 significantly inhibited CRC cell proliferation both in vitro and in vivo.
CONCLUSION: Our study demonstrated that SPRY4 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that SPRY4 may be a potential diagnostic and prognostic target in patients with colorectal cancer.

Zu C, Liu T, Zhang G
MicroRNA-506 Inhibits Malignancy of Colorectal Carcinoma Cells by Targeting LAMC1.
Ann Clin Lab Sci. 2016; 46(6):666-674 [PubMed] Related Publications
OBJECTIVE: To investigate the effects of microRNA-506 (miR-506) on malignancy of colorectal carcinoma (CRC) cells and to elucidate the underlying mechanism.
METHODS: Human colorectal carcinoma cell lines SW480, SW620, HCT116, and HT29 were served as model. Five experimental groups are established in this study, including cell control, pcDNA3 blank vector control, miR-506 over-expression, pSIH1 blank vector control, and miR-506 suppression groups. Quantitative reverse transcription PCR (qRT-PCR) assay was performed to measure miR-506 level. Transwell, Cell counting kit8 (CCK-8), and colony formation assays were performed to detect migration and invasion, viability, and colony formation abilities of CRC cell lines, respectively. Furthermore, bioinformatics method was applied to predict potential target genes of miR-506. Green fluorescent protein (GFP) reporter assays were used to verify the direct regulation of miR-506 on target mRNA in CRC cell lines. The LAMC1 mRNA and protein levels were detected by qRT-PCR and Western blot, respectively.
RESULTS: In the CRC cell lines, miR-506 level increased in the miR-506 over-expression group (P<0.05), compared with the blank vector control group. In the miR-506 over-expression group, cellular viability was significantly reduced (P<0.05). Migrated and invasive cell numbers and cell colony numbers were decreased (P<0.05). LAMC1 mRNA and protein levels in the miR-506 over-expression groups were lower than those in the control groups (P<0.05). However, there were no difference on the above indexes between pSIH1 blank vector control and miR-506 suppression groups.
CONCLUSION: miR-506 acts as a tumor suppressor and inhibits malignancy of colorectal cancer cells through directly targeting LAMC1.

Hu J, Yan WY, Xie L, et al.
Coexistence of MSI with KRAS mutation is associated with worse prognosis in colorectal cancer.
Medicine (Baltimore). 2016; 95(50):e5649 [PubMed] Free Access to Full Article Related Publications
Kristen rat sarcoma viral oncogene homolog (KRAS) and microsatellite instability (MSI) are prognostic markers of colorectal cancer (CRC). However, the clinical value is still not fully understood, when giving the consideration to both the molecular makers. Five hundred fifty-one patients with CRC were retrospectively assessed by determining their clinicopathological features. KRAS mutations were detected by polymerase chain reaction. MSI, a defect in the mismatch repair (MMR) system, was detected by immunohistochemistry. The prognostic value of KRAS in combination with MSI was studied. Among 551 CRC patients, mutations in KRAS codon 12 and KRAS codon 13 were detected in 34.5% and 10.5% of patients, respectively. Four hundred one tumors were randomly selected to detect for MMR proteins expression. In this analysis, 30 (7.5%) tumors that had at least 1 MMR protein loss were defined as MMR protein-deficient (MMR-D), and the remaining tumors were classed as MMR protein-intact (MMR-I). According to KRAS mutation and MSI status, CRC was classified into 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group4 had the best prognosis. In conclusion, combination status of KRAS and MSI status may be used as a prognostic biomarker for CRC patient, if validated by larger studies.

Simone G
Stochastic phenotypic interconversion in tumors can generate heterogeneity.
Eur Biophys J. 2017; 46(2):189-194 [PubMed] Related Publications
Phenotype variations define heterogeneity in biological and molecular systems, and play a crucial mechanistic role, and heterogeneity has been demonstrated in tumor cells. In this work, cells from blood of patients affected by colon cancer were analyzed and sorted using a microfluidic assay based on galactose-active moieties and incubated for culturing in severe combined immunodeficiency (SCID) mice. Based on the results of these experiments, a model based on Markov theory is implemented and discussed to explain the equilibrium existing between phenotypes of cell subpopulations sorted using the microfluidic assay. In combination with the experimental results, the model has many implications for tumor heterogeneity; For example, it displays interconversion of phenotypes, confirming the experiments. Such interconversion generates metastatic cells and implies that targeting circulating tumor cells (CTC) will not be an efficient method for prevention of tumor recurrence. Most importantly, understanding the transitions between cell phenotypes in the cell population can improve understanding of tumor generation and growth.

Sefrioui D, Mauger F, Leclere L, et al.
Comparison of the quantification of KRAS mutations by digital PCR and E-ice-COLD-PCR in circulating-cell-free DNA from metastatic colorectal cancer patients.
Clin Chim Acta. 2017; 465:1-4 [PubMed] Related Publications
Circulating cell-free DNA (ccfDNA) bears great promise as biomarker for personalized medicine, but ccfDNA is present only at low levels in the plasma or serum of cancer patients. E-ice-COLD-PCR is a recently developed enrichment method to detect and identify mutations present at low-abundance in clinical samples. However, recent studies have shown the importance to accurately quantify low-abundance mutations as clinically important decisions will depend on certain mutation thresholds. The possibility for an enrichment method to accurately quantify the mutation levels remains a point of concern and might limit its clinical applicability. In the present study, we compared the quantification of KRAS mutations in ccfDNA from metastatic colorectal cancer patients by E-ice-COLD-PCR with two digital PCR approaches. For the quantification of mutations by E-ice-COLD-PCR, cell lines with known mutations diluted into WT genomic DNA were used for calibration. E-ice-COLD-PCR and the two digital PCR approaches showed the same range of the mutation level and were concordant for mutation levels below the clinical relevant threshold. E-ice-COLD-PCR can accurately detect and quantify low-abundant mutations in ccfDNA and has a shorter time to results making it compatible with the requirements of analyses in a clinical setting without the loss of quantitative accuracy.

Wang W, Zhang G, Yang J, et al.
Digital gene expression profiling analysis of DNA repair pathways in colon cancer stem population of HT29 cells.
Acta Biochim Biophys Sin (Shanghai). 2017; 49(1):90-100 [PubMed] Related Publications
Cancer stem cells (CSCs) contribute to the relapse and development of new neoplasm lesions. While most available clinical approaches, such as chemical and radiation therapies, will kill the majority of cancer cells, they do not kill them all. Some resisting cells, like CSCs, are able to survive due to their excellent self-maintaining capabilities, even in challenging environments. In the present study, we investigated the mRNA level of DNA repair genes of colon CSCs from the HT29 cell line in response to single-strand damage and double-strand breaks, as well as the evident upregulation of key genes in base excision repair, mismatch repair, non-homologous end-joining, and homologous recombination pathways in these cells. Digital gene expression analysis identified upregulated genes in CD44(+) HT29 cells that may play important roles in DNA repair. Our results reveal that colon CSCs bear efficient DNA repair abilities, which might explain the survival of colon CSCs after repeated chemical and radiation therapy.

Zhou J, Li X, Wu M, et al.
Knockdown of Long Noncoding RNA GHET1 Inhibits Cell Proliferation and Invasion of Colorectal Cancer.
Oncol Res. 2016; 23(6):303-309 [PubMed] Related Publications
Emerging evidence has identified the vital role of long noncoding RNAs (lncRNAs) in the development of colorectal cancer. In this study, we aimed to investigate the role of lncRNA gastric carcinoma highly expressed transcript 1 (GHET1) in colorectal cancer. We analyzed the expression of GHET1 in colorectal cancer (CRC) tissues by using ISH. We found that GHET1 expression was significantly increased in the CRC samples compared with adjacent tissues. Furthermore, the cancer tissues had higher GHET1 mRNA levels than their matched adjacent tissues. GHET1 expression was also significantly increased in the CRC cell lines compared with human normal colon epithelial cells. Downregulation of GHET1 mediated by shRNA suppressed the proliferation, cell cycle arrest, migration, and invasion of colorectal cancer cells in vitro. In addition, inhibition of GHET1 reversed the epithelialmesenchymal transition in colorectal cancer cell lines. Taken together, our results suggest the potential use of GHET1 as a therapeutic target of colorectal cancer.

Sambuudash O, Kim HM, Jo H, et al.
Molecular characteristics of colorectal serrated polyps and hyperplastic polyps: A STROBE compliant article.
Medicine (Baltimore). 2016; 95(49):e5592 [PubMed] Free Access to Full Article Related Publications
The serrated neoplasia pathway of colorectal carcinogenesis is characterized by BRAF mutation and aberrant DNA methylation, which have not been reported on Korean patients. The aim of this study was to investigate BRAF mutation and DNA methylation in colorectal serrated polyps and the right colon.Between 2005 and 2013, 146 colon polyps (47 tubular adenomas [TAs], 53 traditional serrated adenomas [TSAs], 17 sessile serrated adenomas/polyps [SSAs], and 29 hyperplastic polyps in the proximal colon [PHPs]) were collected from patients. Paraffin-embedded colon polyp tissue was used for DNA extraction. BRAF V600E mutation was identified through polymerase chain reaction (PCR) and pyrosequencing assay. The methylation status of the long interspersed nucleotide element-1, insulin-like growth factor binding protein 7 (IGFBP7), mutL homolog 1 (hMLH1), and CD133 genes were evaluated through disulfite conversion, PCR, and pyrosequencing assay.BRAF V600E mutation was found in 2.1% of TAs, 47.2% of TSAs, 41.2% of SSAs, and 20.7% of PHPs. TSA and SSA had higher BRAF mutation rates than did TA (P < 0.0001). TSA had higher BRAF mutation rates than did PHP (P = 0.018). IGFBP7 hypermethylation was found in 17% of TAs, 37.7% of TSAs, 88.2% of SSAs, and 37.5% of PHPs. TSA and SSA had higher hypermethylation of IGFBP7 than did TA (P = 0.021 and P < 0.0001, respectively). SSA had higher hypermethylation of IGFBP7 than did PHP (P = 0.002). hMLH1 hypermethylation was found in 2.1% of TAs, 5.7% of TSAs, 0% of SSAs, and 0% of PHPs. CD133 hypermethylation was found in 21.3% of TAs, 9.4% of TSAs, 35.3% of SSAs, and 17.4% of PHPs.BRAF mutation and methylation in TSA and SSA are different from those in PHP in Koreans. These findings suggested that PHP may have different molecular characteristics compared with other serrated polyps.

Zhang S, Wang Z, Shan J, et al.
Nuclear expression and/or reduced membranous expression of β-catenin correlate with poor prognosis in colorectal carcinoma: A meta-analysis.
Medicine (Baltimore). 2016; 95(49):e5546 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The differential subcellular localizations of β-catenin (including membrane, cytoplasm, and nucleus) play different roles in the progression of colorectal cancer (CRC). However, the correlation between each subcellular localization of β-catenin and the prognosis of CRC patients remains undetermined.
METHODS: Systematic strategies were applied to search for eligible published studies in the PubMed, Embase, and Web of Science databases. The correlation between each subcellular localizations of β-catenin expression and patients' clinicopathological features or prognosis was analyzed.
RESULTS: Finally, this meta-analysis, including 6238 cases from 34 studies, revealed that β-catenin overexpression in the nucleus (HR: 1.50[95% CI: 1.08-2.10]) or reduced expression of β-catenin in the membrane (HR: 1.33[95% CI: 1.15-1.54]) significantly correlated with lower 5-year overall survival (OS). Conversely, overexpression of β-catenin in the cytoplasm (HR: 1.00[95% CI: 0.85-1.18]) did not show significant association with 5-year OS.
CONCLUSION: This study suggested that β-catenin overexpression in the nucleus or reduced expression in the membrane, but not its overexpression in cytoplasm, could serve as a valuable prognostic predictor for CRC. However, additional large and well-designed prospective studies are required to verify our results.

Kameyama H, Shimada Y, Ichikawa H, et al.
[New Classification for Advanced Colorectal Cancer Using CancerPlex®Genomic Tests].
Gan To Kagaku Ryoho. 2016; 43(11):1361-1365 [PubMed] Related Publications
Recently, targeted drugs have been developed for the treatment of colorectal cancer(CRC). Among targets, it is well known that KRAS mutations are associated with resistance to epidermal growth factor receptor(EGFR)monoclonal antibodies. However, response rates using anti-EGFR monotherapy for CRC were less than 20-30% in previous clinical studies. Thus, because the RAS/MAP2K/MAPK and PI3K/AKT pathways are associated with CRC resistance to chemotherapy, we analyzed gene mutations in Stage IV CRC patients using a genomic test(CancerPlex®). Medical records were reviewed for 112 patients who received treatment for CRC between 2007 and 2015 in Niigata University Medical and Dental Hospital or Niigata Cancer Center Hospital. There were 66 male and 46 female patients, and their median age was 62.5(range, 30-86) years. Cluster analyses were performed in 110 non-hypermutated Japanese CRC patients using Euclidean distance and Ward's clustering method, and 6 typical groups were identified. Among these, patients with all wild-type actionable genes benefited from anti-EGFR therapies. The expense of targeted drugs warrants consideration of cost-effectiveness during treatment decision-making for advanced CRC patients. To this end, based on the genetic information on CRC, it is possible to develop precision medicine using CancerPlex®.

Chen W, Ding J, Jiang L, et al.
DNA copy number profiling in microsatellite-stable and microsatellite-unstable hereditary non-polyposis colorectal cancers by targeted CNV array.
Funct Integr Genomics. 2017; 17(1):85-96 [PubMed] Related Publications
About half of hereditary non-polyposis colorectal cancers (HNPCCs) fulfilling the Amsterdam criteria (AC) do not display evidence of mismatch repair defects, and the difference between microsatellite-stable (MSS) and microsatellite-unstable HNPCC remains poorly understood. The study was to compare overall copy number variation (CNV) and loss of heterozygosity (LOH) of the entire genome in HNPCCs with MSS and microsatellite-instability (MSI) using the Cytoscan HD Array. This was a study carried out in samples from 20 patients with MSS HNPCC and four patients with MSI HNPCC from the Fudan University Shanghai Cancer Center (China). The microsatellite status was examined using a panel of microsatellite markers. MMR expression status was evaluated by immunohistochemistry. Tumor samples were analyzed with the Genome-Wide Human CytoScan HD Array. CNV and LOH were determined. Fourteen specific CNVs (eight gains: 5p13.1, 7p13, 7q22.3, 8q11.21, 8q12.2, 19q13.11, 20q11.21, and 20q11.23; and six losses: 8p22, 8p23.1, 8p23.1, 17p13.1, 17p13.2, and 18q21.3) were associated with MSS HNPCC. Of these 14 CNVs, gain on 8q12.2 and loss on 17p13.1 were novel. The total length of 8q gains and 20q gains were greater in MSS tumors than in MSI (P < 0.05). The presence of similar levels of copy-neutral-LOH in MSS (31.7%) and MSI (29.7%) HNPCC suggested that unknown DNA repair genes might be involved in the tumorigenesis of MSS HNPCC. MSS HNPCC is a genetically specific population with increased CNV, which are different from MSI HNPCC. The results may help to clarify the genetic basis of MSS HNPCC tumorigenesis.

Kasagi Y, Oki E, Ando K, et al.
The Expression of CCAT2, a Novel Long Noncoding RNA Transcript, and rs6983267 Single-Nucleotide Polymorphism Genotypes in Colorectal Cancers.
Oncology. 2017; 92(1):48-54 [PubMed] Related Publications
Colon cancer-associated transcription 2 (CCAT2) was recently identified as a novel long noncoding RNA transcript encompassing the single-nucleotide polymorphism rs6983267. CCAT2 is overexpressed in colorectal cancer (CRC) where it promotes tumor growth, metastasis, and chromosomal instability, although the clinical relevance of this enhanced expression is unknown. In this retrospective study, CCAT2 expression was evaluated using real-time polymerase chain reaction in 149 CRC patients, and its associations with clinicopathological characteristics, outcome, rs6983267 genotypes, microsatellite status, DNA ploidy, and BubR1 expression were analyzed. CCAT2 expression in cancer tissue was significantly higher than in noncancer tissue (p < 0.001), particularly in cases of metastatic cancer (p < 0.001). However, relative CCAT2 expression levels and rs6983267 genotypes were not correlated with clinicopathological features or patient prognosis. CRC cases demonstrating high CCAT2 expression were all microsatellite stable (p < 0.005). Together, this indicates that CCAT2 expression was associated with microsatellite-stable CRC.

Kacerovska D, Drlik L, Slezakova L, et al.
Cutaneous Sebaceous Lesions in a Patient With MUTYH-Associated Polyposis Mimicking Muir-Torre Syndrome.
Am J Dermatopathol. 2016; 38(12):915-923 [PubMed] Related Publications
A 76-year-old white male with a history of adenocarcinoma of the rectosigmoideum and multiple colonic polyps removed at the age of 38 and 39 years by an abdominoperitoneal amputation and total colectomy, respectively, presented with multiple whitish and yellowish papules on the face and a verrucous lesion on the trunk. The lesions were surgically removed during the next 3 years and a total of 13 lesions were investigated histologically. The diagnoses included 11 sebaceous adenomas, 1 low-grade sebaceous carcinoma, and 1 squamous cell carcinoma. In some sebaceous lesions, squamous metaplasia, intratumoral heterogeneity, mucinous changes, and peritumoral lymphocytes as sometimes seen in sebaceous lesions in Muir-Torre syndrome were noted. Mutation analysis of the peripheral blood revealed a germline mutation c.692G>A,p.(Arg231His) in exon 9 and c.1145G>A, p.(Gly382Asp) in exon 13 of the MUTYH gene. A KRAS mutation G12C (c.34G>T, p.Gly12Cys) was detected in 1 sebaceous adenoma and a NRAS mutation Q61K (c.181C>A, p.Gln61Lys) was found in 2 other sebaceous adenomas. No germline mutations in MLH1, MSH2, MSH6 and PMS2 genes, no microsatellite instability, no aberrant methylation of MLH1 promoter, and no somatic mutations in MSH2 and MSH6 were found. An identical MUTYH germline mutation was found in the patient's daughter. Despite striking clinicopathological similarities with Muir-Torre syndrome, the molecular biologic testing confirmed the final diagnosis of MUTYH-associated polyposis.

Sartore-Bianchi A, Siena S, Tonini G, et al.
Overcoming dynamic molecular heterogeneity in metastatic colorectal cancer: Multikinase inhibition with regorafenib and the case of rechallenge with anti-EGFR.
Cancer Treat Rev. 2016; 51:54-62 [PubMed] Related Publications
In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient survival has been significantly improved with the introduction of monoclonal antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or panitumumab) in first- and second-line therapies. However, all patients treated with chemotherapy and targeted therapies will eventually relapse, and recently the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in other genes has been shown to jeopardize response to EGFR blockade. In chemorefractory patients, multikinase inhibition with regorafenib has proved to be effective and rechallenge with chemotherapy or anti-EGFR agents is empirically pursued. This review will critically discuss how the evolving knowledge of mechanisms of resistance driven by intratumoural dynamic molecular heterogeneity can impact on rational choice of treatments in this setting.

Xie T, Huang M, Wang Y, et al.
MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer.
Cell Physiol Biochem. 2016; 40(1-2):62-76 [PubMed] Related Publications
Chemotherapy and targeted therapy are the main options for andvanced colorectal cancer (CRC). However, resistance to these therapies is a major challenge in the clinic. Understanding molecular mechanisms and developing effective strategies against the drug resistance are highly desired. Increasing evidence has revealed that microRNAs (miRNAs) are closely linked to drug resistance in CRC. The explosion of knowledge in this field has brought forward new predictive and therapeutic opportunities. In this review, we systemically summarize the roles of miRNAs as regulators, tissue or circulating biomarkers, and therapeutics in the CRC resistance to 5-fluorouracil (5-FU), oxaliplatin and anti-EGFR therapy. We also discuss the potential unsettled issues and future directions concerning these processes.

Gelsomino F, Barbolini M, Spallanzani A, et al.
The evolving role of microsatellite instability in colorectal cancer: A review.
Cancer Treat Rev. 2016; 51:19-26 [PubMed] Related Publications
Microsatellite instability (MSI) is a molecular marker of a deficient mismatch repair (MMR) system and occurs in approximately 15% of colorectal cancers (CRCs), more frequently in early than late-stage of disease. While in sporadic cases (about two-thirds of MSI-H CRCs) MMR deficiency is caused by an epigenetic inactivation of MLH1 gene, the remainder are associated with Lynch syndrome, that is linked to a germ-line mutation of one of the MMR genes (MLH1, MSH2, MSH6, PMS2). MSI-H colorectal cancers have distinct clinical and pathological features such as proximal location, early-stage (predominantly stage II), poor differentiation, mucinous histology and association with BRAF mutations. In early-stage CRC, MSI can select a group of tumors with a better prognosis, while in metastatic disease it seems to confer a negative prognosis. Although with conflicting results, a large amount of preclinical and clinical evidence suggests a possible resistance to 5-FU in these tumors. The higher mutational load in MSI-H CRC can elicit an endogenous immune anti-tumor response, counterbalanced by the expression of immune inhibitory signals, such as PD-1 or PD-L1, that resist tumor elimination. Based on these considerations, MSI-H CRCs seem to be particularly responsive to immunotherapy, such as anti-PD-1, opening a new era in the treatment landscape for patients with metastatic CRC.

Ozemir IA, Aslan S, Eren T, et al.
The Diagnostic and Prognostic Significance of Serum Neutrophil Gelatinase-Associated Lipocalin Levels in Patients with Colorectal Cancer.
Chirurgia (Bucur). 2016 Sept-Oct; 111(5):414-421 [PubMed] Related Publications
AIM OF THE STUDY: Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker that is stored in neutrophil granules. Recent studies revealed that NGAL expression increases in tissue samples of patients with inflammatory gastrointestinal system diseases and cancers. The aim of this study was to evaluate the diagnostic and predictive significance of plasma NGAL levels in various stages of adenoma-carcinoma sequence of colorectal cancer. Materials and Methods: Eighty cases were included in the study and separated into 3 groups. "Cancer Group" consisted of 27 colorectal cancer patients who underwent curative resection, whereas 24 patients with colorectal adenomatous polyps detected by colonoscopy were classified as the "Polyp Group", and 29 patients with normal colonoscopy findings were classified as the "Control Group". The serum NGAL, CEA and CA19-9 levels and histopathology findings were determined. Results: The mean plasma NGAL levels for control group, polyp group and cancer group were found to be 91.5 ng/ml, 139.6ng/ml and 184.3ng/ml, respectively. Plasma NGAL levels were found to be significantly higher in cancer group compared to the control group (p:0.006). Plasma NGAL levels were detected statistically significant and positive correlated with tumor diameter and number of metastatic lymph nodes (p:0.047, r:%38.6 and p:0.026, r:%42.8, respectively) in cancer group. Conclusions: We are of the opinion that pre-operative plasma NGAL level is a potential diagnostic biomarker for colorectal cancer patients. Although more comprehensive studies are needed for definitive judgments, serum NGAL levels may be used as a diagnostic and/or predictive biomarker for lymph node metastasis in patients with colorectal cancer.

Recurrent Structural Abnormalities

Selected list of common recurrent structural abnormalities

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

del(8p) in Colorectal Cancers [incl del(8q21)]

Lerebours F, Olschwang S, Thuille B, et al.
Deletion mapping of the tumor suppressor locus involved in colorectal cancer on chromosome band 8p21.
Genes Chromosomes Cancer. 1999; 25(2):147-53 [PubMed] Related Publications
Several somatic genetic alterations have been described in colorectal carcinoma (CRC). Recurrent chromosomal deletions have suggested the presence of tumor suppressor genes (TSG) specifically involved in colorectal carcinogenesis. For one of them, two non-overlapping regions have been proposed on the short arm of chromosome 8, encompassing the LPL and NEFL genes. The short arm of chromosome 8 has been extensively studied in colorectal cancer and in other cancer types. Both regions have been reported as candidate loci for a TSG. In order to delineate a reliable region of deletional overlap on chromosome arm 8p in CRC, a series of 365 CRC samples was selected for the absence of microsatellite instability (RER, replication error); tumor and normal matched DNAs were studied for 54 microsatellite polymorphisms distributed on 8p using multiplex-PCR amplification. After purification of tumor nuclei by flow cytometry based on either the abnormal DNA index or the presence of a high expression of cytokeratin, complete allelic losses on 8p were observed in 48% of cases. Measurement of the DNA index showed that 88% of RER tumors were hyperploid. Complete allelic losses of only part of the short arm were observed on 26 occasions. These data allowed us to define a 1 cM interval of common deletion, flanked by the loci D8S1771 and NEFL, where a putative TSG may be localized.

Fujiwara Y, Emi M, Ohata H, et al.
Evidence for the presence of two tumor suppressor genes on chromosome 8p for colorectal carcinoma.
Cancer Res. 1993; 53(5):1172-4 [PubMed] Related Publications
We have examined loss of heterozygosity on the short arm of chromosome 8 in 133 colorectal carcinomas, using 20 restriction fragment length polymorphism markers. Loss of heterozygosity was observed in 58 (44%) of 131 tumors that were informative with at least one locus. Among these 58, 32 revealed a partial or interstitial deletion of chromosome 8p. Detailed deletion mapping of chromosome 8p in these tumors identified two distinct, commonly deleted regions. One was located between markers C18-266 and pSVL-LPL at 8p23.2-8p22, and the other between CI8-319 and CI8-494 at 8p21.3-8p11.22. The genetic lengths of these two intervals were estimated to be 28 and 18 cM, respectively. The results suggest that at least two tumor suppressor genes associated with colorectal carcinomas are present on chromosome 8p. Correlation of loss of heterozygosity on 8p to the clinicopathological stage was also detected, suggesting that inactivation of a tumor suppressor gene(s) on 8p plays a role in progression of colorectal carcinomas.

18q Loss in Colorectal Cancer

Ogunbiyi OA, Goodfellow PJ, Herfarth K, et al.
Confirmation that chromosome 18q allelic loss in colon cancer is a prognostic indicator.
J Clin Oncol. 1998; 16(2):427-33 [PubMed] Related Publications
PURPOSE: Recent studies suggest that allelic loss of sequences from the long arm of chromosome 18 may be a useful prognostic indicator in colorectal cancer. The aim of the present study was to confirm whether 18q loss of heterozygosity (LOH) is of prognostic value in patients with colon cancer.
METHODS: Genomic DNA was prepared from archival tumor and corresponding normal tissue specimens from 151 patients who had undergone potentially curative surgery for adenocarcinoma of the colon. Polymerase chain reaction (PCR) was used to assess allelic loss of five chromosome 18q microsatellite markers in the tumors. The relationship between allelic loss and disease-free and disease-specific survival was investigated.
RESULTS: LOH was detected in 67 of 126 tumors. Chromosome 18q allelic loss was a negative prognostic indicator of both disease-free (relative risk [RR], 1.65; P = .01) and disease-specific survival (RR, 2.0; P = .003). 18q loss was also associated with significantly reduced disease-free and disease-specific survival in patients with stage II (P = .05 and P = .0156) and III (P = .038 and P = .032) disease.
CONCLUSION: Chromosome 18q allelic loss is a prognostic marker in colorectal cancers. Chromosome 18 LOH studies may be useful in identifying patients with stage II disease who are at high risk for recurrence, and as such might benefit from adjuvant chemotherapy.

Lindforss U, Fredholm H, Papadogiannakis N, et al.
Allelic loss is heterogeneous throughout the tumor in colorectal carcinoma.
Cancer. 2000; 88(12):2661-7 [PubMed] Related Publications
BACKGROUND: Loss of heterozygosity (LOH) at 17p and 18q in colorectal carcinoma has been depicted as a potential prognostic marker for the disease. However, conclusions vary among reports, and evidence of clinically useful genetic prognostic markers is still lacking. As a rule, single biopsies are used. In this study, the authors hypothesized that an important cause of earlier contradictory results was the heterogeneity of colorectal neoplasms.
METHODS: In this study, DNA originating in each quadrant of tumors from 64 patients with colorectal carcinoma was analyzed. Microsatellite markers for chromosome 18q and 17p were amplified by polymerase chain reaction and automatically analyzed.
RESULTS: The authors found that, regardless of stage, LOH and non-LOH in both 17p and 18q varied among biopsies within the tumors in a random fashion. LOH in 18q was detected in all 4 quadrants in 22% and in 1 of 4, 2 of 4, or 3 of 4 quadrants in 56% of the tumors, whereas 22% of the tumors were homogeneously without LOH in 18q. LOH 17p was distributed similarly throughout the tumors and was present in 1 of 4, 2 of 4, or 3 of 4 of the quadrants in 44%. The authors also reexamined a subset of tumors by subdividing one biopsy from each into four. Analysis of the microsatellite markers then yielded identical results. No correlation between the degree of LOH status and patient survival was observed.
CONCLUSIONS: LOH status within a colorectal tumor is extensively heterogeneous. However, it is more homologous on a lower macroscopic level. For relevant genetic analysis, multiple biopsies and DNA sampling preceded by careful morphologic examination must be standard in the preparation of DNA.

LOH 17p in Colorectal Cancer

Khine K, Smith DR, Goh HS
High frequency of allelic deletion on chromosome 17p in advanced colorectal cancer.
Cancer. 1994; 73(1):28-35 [PubMed] Related Publications
BACKGROUND: Colorectal cancers often show allelic loss of chromosomes 5q and 17p, regions where the tumor suppressor genes p53 and adenomatous polyposis coli are known to reside. Currently, the inactivation of tumor suppressor genes and the activation of oncogenes are considered major events involved in tumor development. According to a recent genetic model, ras gene mutations and allelic deletion of chromosome 5q are early changes, whereas chromosome 17p and 18q deletions are late changes in colorectal tumorigenesis. It has been shown that 17p and 18q deletions are associated with an increased tendency of disease dissemination in colorectal cancer. Most of the studies on allelic deletion in colorectal cancer were undertaken with Western population cohorts. The authors examined the association of chromosomes 5q and 17p deletions with clinical parameters, including metastasis in a predominantly Chinese population with a high incidence of colorectal cancer.
METHOD: Allelic deletion was studied with the restriction fragment length polymorphism technique in tumors from 102 and 100 sporadic colorectal cancer cases for chromosomes 5q and 17p, respectively. Probes pi 227 and ECB27 were used for chromosome 5q, and probe YNZ22.1 was used for chromosome 17p.
RESULTS: 5q Deletion was found in 33% of informative cases, whereas 17p deletion was seen in 69% of informative cases. 17p Allelic loss showed significant association with Dukes' Stage D as well as the presence of distant metastasis, whereas 5q deletion showed no such association.
CONCLUSION: Allelic loss on chromosome 17p may be a useful prognostic marker in cases of colorectal cancer.

Takanishi DM, Angriman I, Yaremko ML, et al.
Chromosome 17p allelic loss in colorectal carcinoma. Clinical significance.
Arch Surg. 1995; 130(6):585-8; discussion 588-9 [PubMed] Related Publications
OBJECTIVE: To correlate allelic losses on chromosomes 5q, 8p, 17p, and 18q in colorectal adenocarcinomas with histopathologic features of known prognostic significance.
DESIGN: DNA was extracted from paired samples of 56 fresh-frozen colorectal adenocarcinomas (one classified as Dukes' stage A, 22 as Dukes' stage B, 27 as Dukes' stage C, and six as Dukes'stage D) and adjacent normal mucosa.
SETTING: Specimens were resected at the University of Chicago (Ill) and the University of Padova (Italy) in 1991.
PATIENTS: Samples were obtained from consecutive patients.
INTERVENTIONS: Chromosomes 5q, 8p, 17p, and 18q were studied for loss of heterozygosity by means of Southern hybridization blot analysis of restriction fragment length polymorphisms, and the results were correlated with pathologic tumor stage, degree of differentiation, and lymphatic and/or vascular microinvasion.
RESULTS: Chromosomes 17p and 18q exhibited the highest frequency of loss of heterozygosity (40.6% and 48.8%, respectively). Most of the allelic losses were found in advanced tumors (60% in Dukes' stages C and D combined). A statistically significant correlation was found between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion (P < .01, Fisher's Exact Test).
CONCLUSIONS: There was a significant correlation between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion in colorectal adenocarcinoma, a known stage-independent negative prognostic risk factor. Detection of loss of heterozygosity on chromosome 17p may identify a group of patients who may benefit from more aggressive surgical and/or early adjuvant therapy.

Lindforss U, Fredholm H, Papadogiannakis N, et al.
Allelic loss is heterogeneous throughout the tumor in colorectal carcinoma.
Cancer. 2000; 88(12):2661-7 [PubMed] Related Publications
BACKGROUND: Loss of heterozygosity (LOH) at 17p and 18q in colorectal carcinoma has been depicted as a potential prognostic marker for the disease. However, conclusions vary among reports, and evidence of clinically useful genetic prognostic markers is still lacking. As a rule, single biopsies are used. In this study, the authors hypothesized that an important cause of earlier contradictory results was the heterogeneity of colorectal neoplasms.
METHODS: In this study, DNA originating in each quadrant of tumors from 64 patients with colorectal carcinoma was analyzed. Microsatellite markers for chromosome 18q and 17p were amplified by polymerase chain reaction and automatically analyzed.
RESULTS: The authors found that, regardless of stage, LOH and non-LOH in both 17p and 18q varied among biopsies within the tumors in a random fashion. LOH in 18q was detected in all 4 quadrants in 22% and in 1 of 4, 2 of 4, or 3 of 4 quadrants in 56% of the tumors, whereas 22% of the tumors were homogeneously without LOH in 18q. LOH 17p was distributed similarly throughout the tumors and was present in 1 of 4, 2 of 4, or 3 of 4 of the quadrants in 44%. The authors also reexamined a subset of tumors by subdividing one biopsy from each into four. Analysis of the microsatellite markers then yielded identical results. No correlation between the degree of LOH status and patient survival was observed.
CONCLUSIONS: LOH status within a colorectal tumor is extensively heterogeneous. However, it is more homologous on a lower macroscopic level. For relevant genetic analysis, multiple biopsies and DNA sampling preceded by careful morphologic examination must be standard in the preparation of DNA.

del(1p) in Colorectal Cancer

Matsuzaki M, Nagase S, Abe T, et al.
Detailed deletion mapping on chromosome 1p32-p36 in human colorectal cancer: identification of three distinct regions of common allelic loss.
Int J Oncol. 1998; 13(6):1229-33 [PubMed] Related Publications
Recent studies have suggested the existence of one or several tumor-suppressor genes on chromosome arm 1p in colorectal tumors. To determine the localization of the putative tumor suppressor genes, we performed LOH analysis in 1p in colorectal tumors. A total of 48 paired normal and tumor DNAs of 46 colorectal tumor patients and 21 microsatellite markers on 1p32.1-p36.3 were used for PCR-LOH analysis. Three commonly deleted regions were found: i) 1p36.3 (10-cm); ii) 1p35.1-p36.3 (2-cm); and iii) 1p34.2-p35 (1-cm). These regions overlapped with those reported in several types of tumor. No significant associations were found between LOH and clinicopathologic features. The regions identified in the present study could harbor tumor suppressor genes that would also be associated with several types of human cancer.

Di Vinci A, Infusini E, Nigro S, et al.
Intratumor distribution of 1p deletions in human colorectal adenocarcinoma is commonly homogeneous: indirect evidence of early involvement in colorectal tumorigenesis.
Cancer. 1998; 83(3):415-22 [PubMed] Related Publications
BACKGROUND: Cytogenetics and molecular biology studies have indicated that a large subset of human colorectal adenocarcinomas have distal 1p chromosome arm deletions. The aim of this study was to evaluate the intratumor distribution of 1p deletions under the assumption that homogeneity is an indication of early occurrence.
METHODS: Seventy-nine histologically selected primary sectors (40 superficial and 39 deep) and 3 lymph node metastases obtained from 20 human sporadic adenocarcinomas were analyzed. Interphase two-color fluorescence in situ hybridization (FISH) was applied to cytocentrifuged nuclei using a centromeric probe for chromosome 1 and a telomeric probe mapping to the 1p36 band.
RESULTS: Deletions at 1p were observed in 35 of 82 tumor samples corresponding to 9 of 20 adenocarcinomas analyzed (45%). Seven of the 9 adenocarcinomas with 1p deletions showed an intratumor presence of these aberrations in all the different tumor sectors.
CONCLUSIONS: These data, acquired by FISH interphase cytogenetics, confirm that 1p deletions in colorectal adenocarcinoma are common and suggest that this structural chromosomal aberration occurs mainly as an early event in colorectal tumorigenesis.

LOH 5q in Colorectal Cancer

Arnold CN, Goel A, Niedzwiecki D, et al.
APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q.
Cancer Biol Ther. 2004; 3(10):960-4 [PubMed] Related Publications
INTRODUCTION: Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promoter influences APC silencing. Here we examined the influence of APC methylation on APC expression in tumors with and without LOH at the APC locus.
MATERIAL AND METHODS: 137 sporadic colorectal cancer specimens were investigated for LOH at the 5q locus. The methylation status of the APC promoter was determined by methylation-specific PCR. APC expression was performed by immunohistochemistry.
RESULTS: Expression was reduced or lost in 110 of 137 (80%) tumors and LOH at 5q was found in 13 of 132 (10%) tumors. There was no difference in 5q LOH between tumors with or without intact APC expression. Vice versa, there was no difference in the APC expression in tumors with 5q LOH. Aberrant APC promoter methylation was detected in 33 of 118 (28%) tumors investigated. Of the tumors with 5q LOH for which methylation data were available, 4 of 11 (36%) were methylated versus 28 of 105 (27%) of those without LOH. No difference in methylation was observed in tumors without 5q LOH and normal APC expression and those without 5q LOH and reduced or missing APC expression. Importantly, none of the tumors with 5q LOH and normal APC staining were aberrantly methylated, whereas 50% of the cancers with LOH at 5q and reduced or absent staining were hypermethylated.
CONCLUSIONS: This report suggests that tumors with 5q LOH and reduced APC expression are more frequently hypermethylated at the APC promoter compared to those tumors with 5q LOH and normal APC expression. The association among APC promoter methylation status, 5q LOH, and reduced or lost APC expression suggests that de novo methylation plays an important role as a "second hit" in silencing APC expression in colorectal neoplasia.

Sugai T, Habano W, Nakamura S, et al.
Allelic losses of 17p, 5q, and 18q loci in diploid and aneuploid populations of multiploid colorectal carcinomas.
Hum Pathol. 2000; 31(8):925-30 [PubMed] Related Publications
17p, 5q, and 18q allelic losses are involved in the pathogenesis and progression of colorectal carcinoma, and DNA aneuploidy in this type of cancer is thought to result from alterations of these chromosomal loci. However, genetic differences between diploid and aneuploid populations of multiploid carcinoma, defined as the coexistence of diploid and aneuploid populations in the same area, remain unclear. The differences in 17p, 5q, and 18q allelic losses between the diploid and aneuploid populations in 24 sporadic DNA multiploid colorectal carcinomas were analyzed by use of crypt isolation coupled with DNA cytometric sorting and polymerase chain reaction assay. 17p Allelic loss was observed in 7 of 22 diploid populations excluding 1 case of microsatellite instability but was found in 21 of 23 aneuploid populations. Although 5q allelic loss was detected in only 3 of 22 diploid populations, 13 of 22 aneuploid populations had 5q allelic loss. Losses of the 18q allele were frequently found in aneuploid populations (15 of 20), although no 18q allelic loss was detected in corresponding diploid populations. 17p Allelic losses may play an important role in the progression from a diploid status to an aneuploid status in a specific subset of colorectal cancer. However, 18q or 5q allelic losses do not appear to precede nor to facilitate the aneuploid clonal divergence of cancer cells. Multiploidy is a useful model to study genetic alterations between diploid and aneuploid populations.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. Colorectal Cancers, Cancer Genetics Web: http://www.cancer-genetics.org/X0501.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 10 March, 2017     Cancer Genetics Web, Established 1999