Bladder Cancer - Molecular Biology

Overview

A diverse range of different chromosomal abnormalities have been reported in bladder cancer cells. The most frequently detected genetic abnormality in transitional cell carcinoma (TCC) of bladder is LOH on chromosome 9.

Abnormalities in genes regulating cell cycle control are often seen in advanced bladder cancers, particularly mutations in TP53 and proteins of the G1 checkpoint, especially RB1, CDKN2A (p16) and cyclin D1 (CCND1).

Overexpression of p73 is also common in bladder cancers and some studies have shown that this is associated with disease progression. Differential mucin expression have also been reported in bladder cancers. However, there are conflicting reports about expression specific mucins; MUC1, MUC2 and MUC7.

Uroplakins (membrane proteins) are expressed in both normal and cancerous urothelium and can act as a marker for the detection of metastases and circulating TCC cells.

Gene-Environment Interactions: A number of studies have investigated genes that might modulate the susceptibility to bladder cancer associated with cigarette smoking. These include the NAT1, NAT2, and GSTM1 genes.

See also: Bladder Cancer - clinical resources (22)

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 (307)

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
TP53 17p13.1 P53, BCC7, LFS1, TRP53 -TP53 and Bladder Cancer
509
FGFR3 4p16.3 ACH, CEK2, JTK4, CD333, HSFGFR3EX -FGFR3 and Bladder Cancer
158
CDKN2A 9p21.3 ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A, P16-INK4A Deletion
-CDKN2A deletion in Bladder Cancer
158
BIRC5 17q25 API4, EPR-1 -BIRC5 and Bladder Cancer
139
NAT2 8p22 AAC2, PNAT, NAT-2 -NAT2 and Bladder Cancer
137
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Bladder Cancer
134
TNF 6p21.3 DIF, TNFA, TNFSF2, TNF-alpha -TNF and Bladder Cancer
90
RB1 13q14.2 RB, pRb, OSRC, pp110, p105-Rb, PPP1R130 -RB1 and Bladder Cancer
71
GSTP1 11q13.2 PI, DFN7, GST3, GSTP, FAEES3, HEL-S-22 -GSTP1 and Bladder Cancer
58
CDKN1A 6p21.2 P21, CIP1, SDI1, WAF1, CAP20, CDKN1, MDA-6, p21CIP1 -CDKN1A Expression in Bladder Cancer
48
PPARG 3p25 GLM1, CIMT1, NR1C3, PPARG1, PPARG2, PPARgamma -PPARG and Bladder Cancer
44
CD44 11p13 IN, LHR, MC56, MDU2, MDU3, MIC4, Pgp1, CDW44, CSPG8, HCELL, HUTCH-I, ECMR-III -CD44 and Bladder Cancer
42
PROC 2q13-q14 PC, APC, PROC1, THPH3, THPH4 -PROC and Bladder Cancer
41
XRCC1 19q13.2 RCC -XRCC1 and Bladder Cancer
40
CASP3 4q34 CPP32, SCA-1, CPP32B -CASP3 and Bladder Cancer
38
ERBB2 17q12 NEU, NGL, HER2, TKR1, CD340, HER-2, MLN 19, HER-2/neu -ERBB2 and Bladder Cancer
37
KIT 4q12 PBT, SCFR, C-Kit, CD117 -KIT and Bladder Cancer
34
NAT1 8p22 AAC1, MNAT, NATI, NAT-1 -NAT1 and Bladder Cancer
30
MTOR 1p36.2 FRAP, FRAP1, FRAP2, RAFT1, RAPT1 -MTOR and Bladder Cancer
28
AKT1 14q32.32 AKT, PKB, RAC, CWS6, PRKBA, PKB-ALPHA, RAC-ALPHA -AKT1 and Bladder Cancer
27
PIK3CA 3q26.3 MCM, CWS5, MCAP, PI3K, CLOVE, MCMTC, p110-alpha -PIK3CA and Bladder Cancer
24
AR Xq12 KD, AIS, AR8, TFM, DHTR, SBMA, HYSP1, NR3C4, SMAX1, HUMARA -AR and Bladder Cancer
24
CDKN1B 12p13.1-p12 KIP1, MEN4, CDKN4, MEN1B, P27KIP1 -CDKN1B and Bladder Cancer
23
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 Overexpression
-MUC1 and Bladder Cancer
21
VEGFA 6p12 VPF, VEGF, MVCD1 -VEGF Expression in Bladder Cancer
21
IL10 1q31-q32 CSIF, TGIF, GVHDS, IL-10, IL10A -Interleukin-10 and Bladder Cancer
19
NRAS 1p13.2 NS6, CMNS, NCMS, ALPS4, N-ras, NRAS1 -NRAS and Bladder Cancer
19
H19 11p15.5 ASM, BWS, WT2, ASM1, D11S813E, LINC00008, NCRNA00008 -H19 and Bladder Cancer
18
CD82 11p11.2 R2, 4F9, C33, IA4, ST6, GR15, KAI1, SAR2, TSPAN27 -CD82 and Bladder Cancer
18
FHIT 3p14.2 FRA3B, AP3Aase -FHIT and Bladder Cancer
17
EZH2 7q35-q36 WVS, ENX1, EZH1, KMT6, WVS2, ENX-1, EZH2b, KMT6A -EZH2 and Bladder Cancer
15
CDK4 12q14 CMM3, PSK-J3 -CDK4 and Bladder Cancer
14
DAPK1 9q21.33 DAPK -DAPK1 and Bladder Cancer
13
CDKN2B 9p21 P15, MTS2, TP15, CDK4I, INK4B, p15INK4b -CDKN2B and Bladder Cancer
13
FGFR2 10q26 BEK, JWS, BBDS, CEK3, CFD1, ECT1, KGFR, TK14, TK25, BFR-1, CD332, K-SAM -FGFR2 and Bladder Cancer
12
E2F3 6p22 E2F-3 -E2F3 and Bladder Cancer
12
IGF2 11p15.5 GRDF, IGF-II, PP9974, C11orf43 -IGF2 and Bladder Cancer
12
FGFR1 8p11.23-p11.22 CEK, FLG, HH2, OGD, FLT2, KAL2, BFGFR, CD331, FGFBR, FLT-2, HBGFR, N-SAM, FGFR-1, HRTFDS, bFGF-R-1 -FGFR1 and Bladder Cancer
11
KRT20 17q21.2 K20, CD20, CK20, CK-20, KRT21 -KRT20 and Bladder Cancer
11
DAPK2 15q22.31 DRP1, DRP-1 -DAPK2 and Bladder Cancer
11
ERCC1 19q13.32 UV20, COFS4, RAD10 -ERCC1 and Bladder Cancer
11
TGFA 2p13 TFGA -TGFA and Bladder Cancer
10
GPX1 3p21.3 GPXD, GSHPX1 -GPX1 and Bladder Cancer
10
XIAP Xq25 API3, ILP1, MIHA, XLP2, BIRC4, IAP-3, hIAP3, hIAP-3 -XIAP and Bladder Cancer
10
KRT5 12q13.13 K5, CK5, DDD, DDD1, EBS2, KRT5A -KRT5 and Bladder Cancer
9
FAS 10q24.1 APT1, CD95, FAS1, APO-1, FASTM, ALPS1A, TNFRSF6 -FAS and Bladder Cancer
9
CCNB1 5q12 CCNB -CCNB1 and Bladder Cancer
9
CLMP 11q24.1 ACAM, ASAM, CSBM, CSBS -CLMP and Bladder Cancer
9
TGFBR1 9q22 AAT5, ALK5, ESS1, LDS1, MSSE, SKR4, ALK-5, LDS1A, LDS2A, TGFR-1, ACVRLK4, tbetaR-I -TGFBR1 and Bladder Cancer
9
JUN 1p32-p31 AP1, AP-1, c-Jun -c-Jun and Bladder Cancer
9
AURKA 20q13 AIK, ARK1, AURA, BTAK, STK6, STK7, STK15, AURORA2, PPP1R47 -AURKA and Bladder Cancer
9
ICAM1 19p13.3-p13.2 BB2, CD54, P3.58 -ICAM1 and Bladder Cancer
8
TACC3 4p16.3 ERIC1, ERIC-1 -TACC3 and Bladder Cancer
8
VEGFC 4q34.3 VRP, Flt4-L, LMPH1D -VEGFC and Bladder Cancer
8
TERC 3q26 TR, hTR, TRC3, DKCA1, PFBMFT2, SCARNA19 -TERC and Bladder Cancer
8
CEACAM5 19q13.2 CEA, CD66e -CEACAM5 and Bladder Cancer
8
NME1 17q21.3 NB, AWD, NBS, GAAD, NDKA, NM23, NDPKA, NDPK-A, NM23-H1 -NME1 and Bladder Cancer
8
KRT7 12q13.13 K7, CK7, SCL, K2C7 -KRT7 and Bladder Cancer
7
PDLIM4 5q31.1 RIL -PDLIM4 and Bladder Cancer
7
GAPDH 12p13 G3PD, GAPD, HEL-S-162eP -GAPDH and Bladder Cancer
7
FASLG 1q23 APTL, FASL, CD178, CD95L, ALPS1B, CD95-L, TNFSF6, APT1LG1 -FASLG and Bladder Cancer
7
EPHX1 1q42.1 MEH, EPHX, EPOX, HYL1 -EPHX1 and Bladder Cancer
7
MAPK1 22q11.21 ERK, p38, p40, p41, ERK2, ERT1, ERK-2, MAPK2, PRKM1, PRKM2, P42MAPK, p41mapk, p42-MAPK -MAPK1 and Bladder Cancer
7
HLA-A 6p21.3 HLAA -HLA-A and Bladder Cancer
7
CCR2 3p21.31 CKR2, CCR-2, CCR2A, CCR2B, CD192, CKR2A, CKR2B, CMKBR2, MCP-1-R, CC-CKR-2 -CCR2 and Bladder Cancer
6
EDNRB 13q22 ETB, ET-B, ETB1, ETBR, ETRB, HSCR, WS4A, ABCDS, ET-BR, HSCR2 -EDNRB and Bladder Cancer
6
NOS2 17q11.2 NOS, INOS, NOS2A, HEP-NOS -NOS2 and Bladder Cancer
6
STAG2 Xq25 SA2, SA-2, SCC3B, bA517O1.1 GWS
-STAG2 and Bladder Cancer
6
ARHGDIB 12p12.3 D4, GDIA2, GDID4, LYGDI, Ly-GDI, RAP1GN1, RhoGDI2 -ARHGDIB and Bladder Cancer
6
MAPK3 16p11.2 ERK1, ERT2, ERK-1, PRKM3, P44ERK1, P44MAPK, HS44KDAP, HUMKER1A, p44-ERK1, p44-MAPK -MAPK3 and Bladder Cancer
5
ERCC6 10q11.23 CSB, CKN2, COFS, ARMD5, COFS1, RAD26, UVSS1 -ERCC6 and Bladder Cancer
5
TEP1 14q11.2 TP1, TLP1, p240, TROVE1, VAULT2 -TEP1 and Bladder Cancer
5
MIR10A 17q21.32 MIRN10A, mir-10a, miRNA10A, hsa-mir-10a -miR-10a and Bladder Cancer
5
MALAT1 11q13.1 HCN, NEAT2, PRO2853, LINC00047, NCRNA00047 -MALAT1 and Bladder Cancer
5
BMI1 10p11.23 PCGF4, RNF51, FLVI2/BMI1 -BMI1 and Bladder Cancer
5
AKT2 19q13.1-q13.2 PKBB, PRKBB, HIHGHH, PKBBETA, RAC-BETA -AKT2 and Bladder Cancer
5
MMP3 11q22.2 SL-1, STMY, STR1, CHDS6, MMP-3, STMY1 -MMP3 and Bladder Cancer
5
BIRC7 20q13.3 KIAP, LIVIN, MLIAP, RNF50, ML-IAP -BIRC7 and Bladder Cancer
5
LGALS3 14q22.3 L31, GAL3, MAC2, CBP35, GALBP, GALIG, LGALS2 -LGALS3 and Bladder Cancer
5
TIMP2 17q25 DDC8, CSC-21K -TIMP2 and Bladder Cancer
5
HPRT1 Xq26.1 HPRT, HGPRT -HPRT1 and Bladder Cancer
5
LARS 5q32 LRS, LEUS, LFIS, ILFS1, LARS1, LEURS, PIG44, RNTLS, HSPC192, hr025Cl -LARS and Bladder Cancer
5
RALA 7p15-p13 RAL -RALA and Bladder Cancer
5
LGALS1 22q13.1 GBP, GAL1 -LGALS1 and Bladder Cancer
4
FLT1 13q12 FLT, FLT-1, VEGFR1, VEGFR-1 -FLT1 Expression in Bladder Cancer
4
STAR 8p11.2 STARD1 -STAR and Bladder Cancer
4
COMT 22q11.21 HEL-S-98n -COMT and Bladder Cancer
4
CCNA1 13q12.3-q13 CT146 -CCNA1 and Bladder Cancer
4
MAGEA3 Xq28 HIP8, HYPD, CT1.3, MAGE3, MAGEA6 -MAGEA3 and Bladder Cancer
4
EWSR1 22q12.2 EWS, EWS-FLI1, bK984G1.4 -EWSR1 and Bladder Cancer
4
HAS1 19q13.4 HAS -HAS1 and Bladder Cancer
4
KLF4 9q31 EZF, GKLF -KLF4 and Bladder Cancer
4
S100A9 1q21 MIF, NIF, P14, CAGB, CFAG, CGLB, L1AG, LIAG, MRP14, 60B8AG, MAC387 -S100A9 and Bladder Cancer
4
EREG 4q13.3 ER, Ep, EPR -EREG and Bladder Cancer
4
PIK3R1 5q13.1 p85, AGM7, GRB1, IMD36, p85-ALPHA -PIK3R1 and Bladder Cancer
4
CCR5 3p21.31 CKR5, CCR-5, CD195, CKR-5, CCCKR5, CMKBR5, IDDM22, CC-CKR-5 -CCR5 and Bladder Cancer
4
GSTM3 1p13.3 GST5, GSTB, GTM3, GSTM3-3 -GSTM3 and Bladder Cancer
4
HGF 7q21.1 SF, HGFB, HPTA, F-TCF, DFNB39 -HGF and Bladder Cancer
4
POLB 8p11.2 -POLB and Bladder Cancer
4
FGF1 5q31 AFGF, ECGF, FGFA, ECGFA, ECGFB, FGF-1, HBGF1, HBGF-1, GLIO703, ECGF-beta, FGF-alpha -FGF1 and Bladder Cancer
4
GSTO1 10q25.1 P28, SPG-R, GSTO 1-1, GSTTLp28, HEL-S-21 -GSTO1 and Bladder Cancer
4
LRIG1 3p14 LIG1, LIG-1 -LRIG1 and Bladder Cancer
4
TP73 1p36.3 P73 -TP73 Overexpression in Bladder Cancer
3
RHOA 3p21.3 ARHA, ARH12, RHO12, RHOH12 -RHOA and Bladder Cancer
3
GSTO2 10q25.1 GSTO 2-2, bA127L20.1 -GSTO2 and Bladder Cancer
3
KRT14 17q21.2 K14, NFJ, CK14, EBS3, EBS4 -KRT14 and Bladder Cancer
3
MAGEA1 Xq28 CT1.1, MAGE1 -MAGEA1 and Bladder Cancer
3
FGF4 11q13.3 HST, KFGF, HST-1, HSTF1, K-FGF, HBGF-4 -FGF4 and Bladder Cancer
3
VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and Bladder Cancer
3
UGT2B7 4q13 UGT2B9, UDPGTH2, UDPGT2B7, UDPGT 2B9 -UGT2B7 and Bladder Cancer
3
NOS3 7q36 eNOS, ECNOS -NOS3 and Bladder Cancer
3
LAMC2 1q25-q31 B2T, CSF, EBR2, BM600, EBR2A, LAMB2T, LAMNB2 -LAMC2 and Bladder Cancer
3
MAP2K6 17q24.3 MEK6, MKK6, MAPKK6, PRKMK6, SAPKK3, SAPKK-3 -MAP2K6 and Bladder Cancer
3
CD47 3q13.1-q13.2 IAP, OA3, MER6 -CD47 and Bladder Cancer
3
S100A8 1q21 P8, MIF, NIF, CAGA, CFAG, CGLA, L1Ag, MRP8, CP-10, MA387, 60B8AG -S100A8 and Bladder Cancer
3
FSCN1 7p22 HSN, SNL, p55, FAN1 -FSCN1 and Bladder Cancer
3
MUC7 4q13.3 MG2 -MUC7 and Bladder Cancer
3
MTRR 5p15.31 MSR, cblE -MTRR and Bladder Cancer
3
CALCA 11p15.2 CT, KC, PCT, CGRP, CALC1, CGRP1, CGRP-I -CALCA and Bladder Cancer
3
DICER1 14q32.13 DCR1, MNG1, Dicer, HERNA, RMSE2, Dicer1e, K12H4.8-LIKE -DICER1 and Bladder Cancer
3
XRCC5 2q35 KU80, KUB2, Ku86, NFIV, KARP1, KARP-1 -XRCC5 and Bladder Cancer
3
CDK1 10q21.1 CDC2, CDC28A, P34CDC2 -CDK1 and Bladder Cancer
3
HDAC4 2q37.3 HD4, AHO3, BDMR, HDACA, HA6116, HDAC-4, HDAC-A -HDAC4 and Bladder Cancer
3
MGEA5 10q24.1-q24.3 OGA, MEA5, NCOAT -MGEA5 and Bladder Cancer
3
NOX1 Xq22 MOX1, NOH1, NOH-1, GP91-2 -NOX1 and Bladder Cancer
3
RAF1 3p25 NS5, CRAF, Raf-1, c-Raf, CMD1NN -RAF1 and Bladder Cancer
3
CKS2 9q22 CKSHS2 -CKS2 and Bladder Cancer
3
ACTB 7p22 BRWS1, PS1TP5BP1 -ACTB and Bladder Cancer
3
COL18A1 21q22.3 KS, KNO, KNO1 -COL18A1 and Bladder Cancer
3
PDGFRB 5q33.1 IMF1, IBGC4, JTK12, PDGFR, CD140B, PDGFR1, PDGFR-1 -PDGFRB and Bladder Cancer
3
IGFBP5 2q35 IBP5 -IGFBP5 and Bladder Cancer
3
DEK 6p22.3 D6S231E -DEK and Bladder Cancer
3
HAS3 16q22.1 -HAS3 and Bladder Cancer
3
MMP14 14q11.2 MMP-14, MMP-X1, MT-MMP, MT1MMP, MTMMP1, WNCHRS, MT1-MMP, MT-MMP 1 -MMP14 and Bladder Cancer
3
SFRP2 4q31.3 FRP-2, SARP1, SDF-5 -SFRP2 and Bladder Cancer
3
NCOA1 2p23 SRC1, KAT13A, RIP160, F-SRC-1, bHLHe42, bHLHe74 -NCOA1 and Bladder Cancer
2
RREB1 6p25 HNT, FINB, LZ321, Zep-1, RREB-1 -RREB1 and Bladder Cancer
2
BUB1 2q14 BUB1A, BUB1L, hBUB1 -BUB1 and Bladder Cancer
2
CEACAM1 19q13.2 BGP, BGP1, BGPI -CEACAM1 and Bladder Cancer
2
SMARCA4 19p13.2 BRG1, CSS4, SNF2, SWI2, MRD16, RTPS2, BAF190, SNF2L4, SNF2LB, hSNF2b, BAF190A -SMARCA4 and Bladder Cancer
2
MCM2 3q21 BM28, CCNL1, CDCL1, cdc19, D3S3194, MITOTIN -MCM2 and Bladder Cancer
2
MAP2K4 17p12 JNKK, MEK4, MKK4, SEK1, SKK1, JNKK1, SERK1, MAPKK4, PRKMK4, SAPKK1, SAPKK-1 -MAP2K4 and Bladder Cancer
2
CDKN2D 19p13 p19, INK4D, p19-INK4D -CDKN2D and Bladder Cancer
2
MMP8 11q22.2 HNC, CLG1, MMP-8, PMNL-CL -MMP8 and Bladder Cancer
2
SDC4 20q12 SYND4 -SDC4 and Bladder Cancer
2
NOX4 11q14.3 KOX, KOX-1, RENOX -NOX4 and Bladder Cancer
2
MAD2L1 4q27 MAD2, HSMAD2 -MAD2L1 and Bladder Cancer
2
ITGB3 17q21.32 GT, CD61, GP3A, BDPLT2, GPIIIa, BDPLT16 -ITGB3 and Bladder Cancer
2
HYAL1 3p21.31 MPS9, NAT6, LUCA1, HYAL-1 -HYAL1 and Bladder Cancer
2
FEZ1 11q24.2 -FEZ1 and Bladder Cancer
2
SMAD2 18q21.1 JV18, MADH2, MADR2, JV18-1, hMAD-2, hSMAD2 -SMAD2 and Bladder Cancer
2
S100P 4p16 MIG9 -S100P and Bladder Cancer
2
MBD2 18q21 DMTase, NY-CO-41 -MBD2 and Bladder Cancer
2
RHOBTB2 8p21.3 DBC2 -RHOBTB2 and Bladder Cancer
2
PLAT 8p12 TPA, T-PA -PLAT and Bladder Cancer
2
ANXA1 9q21.13 ANX1, LPC1 -ANXA1 and Bladder Cancer
2
CUL3 2q36.2 CUL-3, PHA2E -CUL3 and Bladder Cancer
2
MMP12 11q22.2 ME, HME, MME, MMP-12 -MMP12 and Bladder Cancer
2
GLI2 2q14 CJS, HPE9, PHS2, THP1, THP2 -GLI2 and Bladder Cancer
2
GLI3 7p13 PHS, ACLS, GCPS, PAPA, PAPB, PAP-A, PAPA1, PPDIV, GLI3FL, GLI3-190 -GLI3 and Bladder Cancer
2
IMP3 15q24 BRMS2, MRPS4, C15orf12 -IMP3 and Bladder Cancer
2
TAGLN 11q23.3 SM22, SMCC, TAGLN1, WS3-10 -TAGLN and Bladder Cancer
2
RAD23B 9q31.2 P58, HR23B, HHR23B -RAD23B and Bladder Cancer
2
CTAG1B Xq28 CTAG, ESO1, CT6.1, CTAG1, LAGE-2, LAGE2B, NY-ESO-1 -CTAG1B and Bladder Cancer
2
NUMB 14q24.3 S171, C14orf41, c14_5527 -NUMB and Bladder Cancer
2
DAB2IP 9q33.1-q33.3 AIP1, AIP-1, AF9Q34, DIP1/2 -DAB2IP and Bladder Cancer
2
RHEB 7q36 RHEB2 -RHEB and Bladder Cancer
2
RRM1 11p15.4 R1, RR1, RIR1 -RRM1 and Bladder Cancer
2
PCDH10 4q28.3 PCDH19, OL-PCDH -PCDH10 and Bladder Cancer
2
UBE2C 20q13.12 UBCH10, dJ447F3.2 -UBE2C and Bladder Cancer
2
BCHE 3q26.1-q26.2 E1, CHE1, CHE2 -BCHE and Bladder Cancer
2
RALB 2q14.2 -RALB and Bladder Cancer
2
IL4 5q31.1 BSF1, IL-4, BCGF1, BSF-1, BCGF-1 -IL4 and Bladder Cancer
2
WWOX 16q23 FOR, WOX1, EIEE28, FRA16D, SCAR12, HHCMA56, PRO0128, SDR41C1, D16S432E -WWOX and Bladder Cancer
2
SPINK1 5q32 TCP, PCTT, PSTI, TATI, Spink3 -SPINK1 and Bladder Cancer
2
MCM5 22q13.1 CDC46, P1-CDC46 -MCM5 and Bladder Cancer
2
NQO2 6p25.2 QR2, DHQV, DIA6, NMOR2 -NQO2 and Bladder Cancer
2
ERCC4 16p13.12 XPF, RAD1, FANCQ, ERCC11 -ERCC4 and Bladder Cancer
2
KISS1R 19p13.3 HH8, CPPB1, GPR54, AXOR12, KISS-1R, HOT7T175 -KISS1R and Bladder Cancer
2
TNFSF15 9q32 TL1, TL1A, VEGI, VEGI192A -TNFSF15 expression in Bladder Cancer
2
ITGB4 17q25 CD104 -ITGB4 and Bladder Cancer
2
HOXD10 2q31.1 HOX4, HOX4D, HOX4E, Hox-4.4 -HOXD10 and Bladder Cancer
2
KLF5 13q22.1 CKLF, IKLF, BTEB2 -KLF5 and Bladder Cancer
2
IRF9 14q11.2 p48, IRF-9, ISGF3, ISGF3G -IRF9 and Bladder Cancer
1
SRPX Xp21.1 DRS, ETX1, SRPX1, HEL-S-83p -SRPX and Bladder Cancer
1
MSI1 12q24 -MSI1 and Bladder Cancer
1
GNL3 3p21.1 NS, E2IG3, NNP47, C77032 -GNL3 and Bladder Cancer
1
DGCR8 22q11.2 Gy1, pasha, DGCRK6, C22orf12 -DGCR8 and Bladder Cancer
1
LASP1 17q11-q21.3 MLN50, Lasp-1 -LASP1 and Bladder Cancer
1
CSF3R 1p35-p34.3 CD114, GCSFR -CSF3R and Bladder Cancer
1
KLK6 19q13.3 hK6, Bssp, Klk7, SP59, PRSS9, PRSS18 -KLK6 and Bladder Cancer
1
CASP5 11q22.3 ICH-3, ICEREL-III, ICE(rel)III -CASP5 and Bladder Cancer
1
IL12B 5q33.3 CLMF, NKSF, CLMF2, IMD28, IMD29, NKSF2, IL-12B -IL12B and Bladder Cancer
1
AIFM1 Xq26.1 AIF, CMT2D, CMTX4, COWCK, NADMR, NAMSD, PDCD8, COXPD6 -AIFM1 and Bladder Cancer
1
LTB 6p21.3 p33, TNFC, TNFSF3 -LTB and Bladder Cancer
1
CEBPB 20q13.1 TCF5, IL6DBP, NF-IL6, C/EBP-beta -CEBPB and Bladder Cancer
1
FABP5 8q21.13 EFABP, KFABP, E-FABP, PAFABP, PA-FABP -FABP5 and Bladder Cancer
1
ITGA4 2q31.3 IA4, CD49D -ITGA4 and Bladder Cancer
1
SLC7A5 16q24.3 E16, CD98, LAT1, 4F2LC, MPE16, hLAT1, D16S469E -SLC7A5 and Bladder Cancer
1
FH 1q42.1 MCL, FMRD, LRCC, HLRCC, MCUL1 -FH and Bladder Cancer
1
PLK2 5q12.1-q13.2 SNK, hSNK, hPlk2 -PLK2 and Bladder Cancer
1
S100A7 1q21 PSOR1, S100A7c -S100A7 and Bladder Cancer
1
SMPD1 11p15.4 ASM, NPD, ASMASE -SMPD1 and Bladder Cancer
1
UGT2B17 4q13 BMND12, UDPGT2B17 -UGT2B17 and Bladder Cancer
1
HSD3B2 1p13.1 HSDB, HSD3B, SDR11E2 -HSD3B2 and Bladder Cancer
1
KLK5 19q13.33 SCTE, KLKL2, KLK-L2 -KLK5 and Bladder Cancer
1
EML4 2p21 C2orf2, ELP120, EMAP-4, EMAPL4, ROPP120 -EML4 and Bladder Cancer
1
MAD1L1 7p22 MAD1, PIG9, TP53I9, TXBP181 -MAD1L1 and Bladder Cancer
1
NRP2 2q33.3 NP2, NPN2, PRO2714, VEGF165R2 -NRP2 and Bladder Cancer
1
PNN 14q21.1 DRS, DRSP, SDK3, memA -PNN and Bladder Cancer
1
ADGRB1 8q24.3 BAI1, GDAIF -BAI1 and Bladder Cancer
1
BUB3 10q26 BUB3L, hBUB3 -BUB3 and Bladder Cancer
1
IL4R 16p12.1-p11.2 CD124, IL4RA, IL-4RA -IL4R and Bladder Cancer
1
CREB3L1 11p11.2 OASIS -CREB3L1 and Bladder Cancer
1
ARF1 1q42 -ARF1 and Bladder Cancer
1
GRASP 12q13.13 TAMALIN -GRASP and Bladder Cancer
1
IL12A 3q25.33 P35, CLMF, NFSK, NKSF1, IL-12A -IL12A and Bladder Cancer
1
IL17A 6p12 IL17, CTLA8, IL-17, IL-17A -IL17A and Bladder Cancer
1
EIF4EBP1 8p12 BP-1, 4EBP1, 4E-BP1, PHAS-I -EIF4EBP1 and Bladder Cancer
1
PPP1R13L 19q13.32 RAI, RAI4, IASPP, NKIP1 -PPP1R13L and Bladder Cancer
1
ALOX5 10q11.2 5-LO, 5LPG, LOG5, 5-LOX -ALOX5 and Bladder Cancer
1
WHSC1L1 8p11.2 NSD3, pp14328 -WHSC1L1 and Bladder Cancer
1
MYOD1 11p15.1 PUM, MYF3, MYOD, bHLHc1 -MYOD1 and Bladder Cancer
1
MTSS1 8p22 MIM, MIMA, MIMB -MTSS1 and Bladder Cancer
1
MCM4 8q11.2 NKCD, CDC21, CDC54, NKGCD, hCdc21, P1-CDC21 -MCM4 and Bladder Cancer
1
AIM1 6q21 ST4, CRYBG1 -AIM1 and Bladder Cancer
1
HTRA1 10q26.3 L56, HtrA, ARMD7, ORF480, PRSS11, CARASIL -HTRA1 and Bladder Cancer
1
FGF19 11q13.3 -FGF19 and Bladder Cancer
1
XRCC6 22q13.2 ML8, KU70, TLAA, CTC75, CTCBF, G22P1 -XRCC6 and Bladder Cancer
1
CYP2A13 19q13.2 CPAD, CYP2A, CYPIIA13 -CYP2A13 and Bladder Cancer
1
LDLR 19p13.2 FH, FHC, LDLCQ2 -LDLR and Bladder Cancer
1
CHRNB4 15q24 -CHRNB4 and Bladder Cancer
1
RCVRN 17p13.1 RCV1 -RCVRN and Bladder Cancer
1
TRAF6 11p12 RNF85, MGC:3310 -TRAF6 and Bladder Cancer
1
TANK 2q24.2 ITRAF, TRAF2, I-TRAF -TANK and Bladder Cancer
1
NONO Xq13.1 P54, NMT55, NRB54, P54NRB, PPP1R114 -NONO and Bladder Cancer
1
AGTR2 Xq22-q23 AT2, ATGR2, MRX88 -AGTR2 and Bladder Cancer
1
BMPR2 2q33-q34 BMR2, PPH1, BMPR3, BRK-3, POVD1, T-ALK, BMPR-II -BMPR2 and Bladder Cancer
1
IL17C 16q24 CX2, IL-17C -IL17C and Bladder Cancer
1
PRC1 15q26.1 ASE1 -PRC1 and Bladder Cancer
1
CXCL11 4q21.2 IP9, H174, IP-9, b-R1, I-TAC, SCYB11, SCYB9B -CXCL11 and Bladder Cancer
1
NRG1 8p12 GGF, HGL, HRG, NDF, ARIA, GGF2, HRG1, HRGA, SMDF, MST131, MSTP131, NRG1-IT2 -NRG1 and Bladder Cancer
1
CBX7 22q13.1 -CBX7 and Bladder Cancer
1
NEFL 8p21 NFL, NF-L, NF68, CMT1F, CMT2E, PPP1R110 -NEFL and Bladder Cancer
1
MSI2 17q22 MSI2H -MSI2 and Bladder Cancer
1
TES 7q31.2 TESS, TESS-2 -TES and Bladder Cancer
1
LHCGR 2p21 HHG, LHR, LCGR, LGR2, ULG5, LHRHR, LSH-R, LH/CGR, LH/CG-R -LHCGR and Bladder Cancer
1
ELN 7q11.23 WS, WBS, SVAS -ELN and Bladder Cancer
1
KIAA1524 3q13.13 p90, CIP2A -KIAA1524 and Bladder Cancer
1
LAMB3 1q32 AI1A, LAM5, LAMNB1, BM600-125KDA -LAMB3 and Bladder Cancer
1
S100B 21q22.3 NEF, S100, S100-B, S100beta -S100B and Bladder Cancer
1
ENDOU 12q13.1 P11, PP11, PRSS26 -ENDOU and Bladder Cancer
1
HDAC6 Xp11.23 HD6, JM21, CPBHM, PPP1R90 -HDAC6 and Bladder Cancer
1
WRN 8p12 RECQ3, RECQL2, RECQL3 -WRN and Bladder Cancer
1
ADH1C 4q23 ADH3 -ADH1C and Bladder Cancer
1
ATP7B 13q14.3 WD, PWD, WC1, WND -ATP7B and Bladder Cancer
1
RIN1 11q13.2 -RIN1 and Bladder Cancer
1
ITGA6 2q31.1 CD49f, VLA-6, ITGA6B -ITGA6 and Bladder Cancer
1
HLA-G 6p21.3 MHC-G -HLA-G and Bladder Cancer
1
TPTE 21p11 CT44, PTEN2 -TPTE and Bladder Cancer
1
NUMA1 11q13.4 NUMA, NMP-22 -NUMA1 and Bladder Cancer
1
EEF1E1 6p24.3 P18, AIMP3 -EEF1E1 and Bladder Cancer
1
TNFRSF25 1p36.2 DR3, TR3, DDR3, LARD, APO-3, TRAMP, WSL-1, WSL-LR, TNFRSF12 -TNFRSF25 and Bladder Cancer
1
EPHB4 7q22 HTK, MYK1, TYRO11 -EPHB4 and Bladder Cancer
1
YWHAZ 8q23.1 HEL4, YWHAD, KCIP-1, HEL-S-3, 14-3-3-zeta -YWHAZ and Bladder Cancer
1
TBX2 17q23.2 -TBX2 and Bladder Cancer
1
S100A1 1q21 S100, S100A, S100-alpha -S100A1 and Bladder Cancer
1
SMARCA2 9p22.3 BRM, SNF2, SWI2, hBRM, NCBRS, Sth1p, BAF190, SNF2L2, SNF2LA, hSNF2a -SMARCA2 and Bladder Cancer
1
BCL2L12 19q13.3 -BCL2L12 and Bladder Cancer
1
TACSTD2 1p32 EGP1, GP50, M1S1, EGP-1, TROP2, GA7331, GA733-1 -TACSTD2 and Bladder Cancer
1
PDCD6 5p15.33 ALG2, ALG-2, PEF1B -PDCD6 and Bladder Cancer
1
FGF7 15q21.2 KGF, HBGF-7 -FGF7 and Bladder Cancer
1
CAV2 7q31.1 CAV -CAV2 and Bladder Cancer
1
HDAC2 6q21 HD2, RPD3, YAF1 -HDAC2 and Bladder Cancer
1
FLNA Xq28 FLN, FMD, MNS, OPD, ABPX, CSBS, CVD1, FLN1, NHBP, OPD1, OPD2, XLVD, XMVD, FLN-A, ABP-280 -FLNA and Bladder Cancer
1
DRD2 11q23.2 D2R, D2DR -DRD2 and Bladder Cancer
1
MUC5B 11p15.5 MG1, MUC5, MUC9, MUC-5B -MUC5B and Bladder Cancer
1
GNAS 20q13.3 AHO, GSA, GSP, POH, GPSA, NESP, SCG6, SgVI, GNAS1, C20orf45 -GNAS and Bladder Cancer
1
PSIP1 9p22.3 p52, p75, PAIP, DFS70, LEDGF, PSIP2 -PSIP1 and Bladder Cancer
1
TYK2 19p13.2 JTK1, IMD35 -TYK2 and Bladder Cancer
1
MEG3 14q32 GTL2, FP504, prebp1, PRO0518, PRO2160, LINC00023, NCRNA00023, onco-lncRNA-83 -MEG3 and Bladder Cancer
1
AMFR 16q21 GP78, RNF45 -AMFR and Bladder Cancer
1
TNKS 8p23.1 TIN1, ARTD5, PARPL, TINF1, TNKS1, pART5, PARP5A, PARP-5a -TNKS and Bladder Cancer
1
GATA2 3q21.3 DCML, IMD21, NFE1B, MONOMAC -GATA2 and Bladder Cancer
1
LRIG3 12q14.1 LIG3 -LRIG3 and Bladder Cancer
1
ESPL1 12q ESP1, SEPA GWS
-ESPL1 and Bladder Cancer
1
DLEC1 3p21.3 F56, DLC1, CFAP81 -DLEC1 and Bladder Cancer
1
HLA-E 6p21.3 MHC, QA1, EA1.2, EA2.1, HLA-6.2 -HLA-E and Bladder Cancer
1
MYCL 1p34.2 LMYC, L-Myc, MYCL1, bHLHe38 -MYCL and Bladder Cancer
1
CASP2 7q34-q35 ICH1, NEDD2, CASP-2, NEDD-2, PPP1R57 -CASP2 and Bladder Cancer
1
PGK1 Xq13.3 PGKA, MIG10, HEL-S-68p -PGK1 and Bladder Cancer
1
IRAK1 Xq28 IRAK, pelle -IRAK1 and Bladder Cancer
1
ANO1 11q13.3 DOG1, TAOS2, ORAOV2, TMEM16A -ANO1 and Bladder Cancer
1
CASP1 11q22.3 ICE, P45, IL1BC -CASP1 and Bladder Cancer
1
S100A3 1q21 S100E -S100A3 and Bladder Cancer
1
FGFR4 5q35.2 TKF, JTK2, CD334 -FGFR4 and Bladder Cancer
1
TBX3 12q24.21 UMS, XHL, TBX3-ISO -TBX3 and Bladder Cancer
1
HOXA13 7p15.2 HOX1, HOX1J -HOXA13 and Bladder Cancer
1
SHMT1 17p11.2 SHMT, CSHMT -SHMT1 and Bladder Cancer
1
ATIC 2q35 PURH, AICAR, AICARFT, IMPCHASE, HEL-S-70p -ATIC and Bladder Cancer
1
RASAL1 12q23-q24 RASAL -RASAL1 and Bladder Cancer
1
KAT5 11q13.1 TIP, ESA1, PLIP, TIP60, cPLA2, HTATIP, ZC2HC5, HTATIP1 -KAT5 and Bladder Cancer
1
OPCML 11q25 OPCM, OBCAM, IGLON1 -OPCML and Bladder Cancer
1
IRF7 11p15.5 IMD39, IRF7A, IRF7B, IRF7C, IRF7H, IRF-7H -IRF7 and Bladder Cancer
1
ACVRL1 12q13.13 HHT, ALK1, HHT2, ORW2, SKR3, ALK-1, TSR-I, ACVRLK1 -ACVRL1 and Bladder Cancer
TUBE1 6q21 TUBE, dJ142L7.2 -TUBE1 and Bladder Cancer
LINC00632 Xq27.1 -RP1-177G6.2 and Bladder Cancer

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

Latest Publications

Zhi Y, Ji H, Pan J, et al.
Downregulated XPA promotes carcinogenesis of bladder cancer via impairment of DNA repair.
Tumour Biol. 2017; 39(2):1010428317691679 [PubMed] Related Publications
Bladder cancer is the most common malignant tumor of urinary system, largely resulting from failure of repair of DNA damage to the environmental insults. The function of XPA in nucleotide excision repair pathway has been well documented. However, participation of XPA in the repair of DNA double-strand break remains unknown. Here, we reported that bladder cancer expressed low XPA levels compared to adjacent non-tumor bladder tissue, and this phenotype was closely associated with chromosomal aberrations. Moreover, downregulated XPA appeared to increase incidence of chromosome aberration. XPA reduction increased cell viability of a bladder cancer cell line RT4, while XPA re-expression decreased the cell viability of RT4 cells. Since high mutation frequency is the basis of mutations of oncogenes and anti-oncogenes, and may be the essence of bladder cancer susceptibility, our study suggests that downregulated XPA may promote carcinogenesis of bladder cancer via impairment of DNA repair.

Wieczorek E, Jablonowski Z, Tomasik B, et al.
Different Gene Expression and Activity Pattern of Antioxidant Enzymes in Bladder Cancer.
Anticancer Res. 2017; 37(2):841-848 [PubMed] Related Publications
The aim of this study was to evaluate the possible role in and contribution of antioxidant enzymes to bladder cancer (BC) etiology and recurrence after transurethral resection (TUR). We enrolled 40 patients with BC who underwent TUR and 100 sex- and age-matched healthy controls. The analysis was performed at diagnosis and recurrence, taking into account the time of recurrence. Gene expression of catalase (CAT), glutathione peroxidase 1 (GPX1) and manganese superoxide dismutase (SOD2) was determined in peripheral blood leukocytes. The activity of glutathione peroxidase 3 (GPX3) was examined in plasma, and GPX1 and copper-zinc containing superoxide dismutase 1 (SOD1) in erythrocytes. SOD2 and GPX1 expression and GPX1 and SOD1 activity were significantly higher in patients at diagnosis of BC in comparison to controls. In patients who had recurrence earlier than 1 year from TUR, CAT and SOD2 expression was lower (at diagnosis p=0.024 and p=0.434, at recurrence p=0.022 and p=0.010), while the GPX1 and GPX3 activity was higher (at diagnosis p=0.242 and p=0.394, at recurrence p=0.019 and p=0.025) compared to patients with recurrence after 1 year from TUR. This study revealed that the gene expression and activity of the antioxidant enzymes are elevated in blood of patients with BC, although a low expression of CAT might contribute to the recurrence of BC, in early prognosis.

Hadami K, Ameziane El Hassani R, Ameur A, et al.
Association between GPX1 Pro189Leu polymorphism and the occurrence of bladder cancer in Morocco.
Cell Mol Biol (Noisy-le-grand). 2016; 62(14):38-43 [PubMed] Related Publications
Worldwide, Bladder cancer is the most frequent male malignancy. It is the third most common male malignancy in Morocco. The risk factors for developing bladder cancer are multiples including dietary conditions, environmental exposure and oxidative stress. GPX1 gene encoding for the human cellular antioxidant enzyme glutathione peroxidase1 is a key factor in the cell detoxification process. GPX1 Pro198Leu polymorphism is associated with a decrease of enzyme activity and may contribute to bladder cancer susceptibility. The present case-control study was planned to assess the presence of GPX1 Pro198Leu polymorphism in Moroccan population to determine whether it is associated with the risk of developing bladder cancer in Moroccan patients. A total of 32 patients with bladder cancer and 40 healthy controls were enrolled. Genotyping of the GPX1 Pro198Leu polymorphism was carried out by PCR amplification and DNA sequencing. Pro198Leu polymorphism was observed in both bladder cancer patients and healthy controls. No significant association between the polymorphism and bladder cancer occurrence was found (Pro/Leu vs. Pro/Pro: p=0.425; Leu vs. Pro: p=0.435). For the analysis of Pro198Leu polymorphism and progression of bladder cancer, no association was observed neither for stages (Pro/Leu vs. Pro/Pro: p=0.500; Leu vs. Pro: p=0.500) nor grades (Pro/Leu vs. Pro/Pro: p=0.415; Leu vs. Pro: p=0.427). Our results clearly showed no significant association between Pro198Leu polymorphism and risk of bladder cancer in our population, suggesting that the effect of this polymorphism on bladder cancer development might be a result of a combination with other genetic alterations and/or non-genetic variables such as diet and lifestyle factors.

Wang CT, Chen TM, Mei CT, et al.
The Functional Haplotypes of CHRM3 Modulate mRNA Expression and Associate with Bladder Cancer among a Chinese Han Population in Kaohsiung City.
Biomed Res Int. 2016; 2016:4052846 [PubMed] Free Access to Full Article Related Publications
Bladder cancer is one of the major cancer types and both environmental factors and genetic background play important roles in its pathology. Kaohsiung is a high industrialized city in Taiwan, and here we focused on this region to evaluate the genetic effects on bladder cancer. Muscarinic acetylcholine receptor M3 (CHRM3) was reported as a key receptor in different cancer types. CHRM3 is located at 1q42-43 which was reported to associate with bladder cancer. Our study attempted to delineate whether genetic variants of CHRM3 contribute to bladder cancer in Chinese Han population in south Taiwan. Five selected SNPs (rs2165870, rs10802789, rs685550, rs7520974, and rs3738435) were genotyped for 30 bladder cancer patients and 60 control individuals and genetic association studies were performed. Five haplotypes (GTTAT, ATTGT, GCTAC, ACTAC, and ACCAC) were found significantly associated with low CHRM3 mRNA level and contributed to increased susceptibility of bladder cancer in Kaohsiung city after rigid 10000 consecutive permutation tests. To our knowledge, this is the first genetic association study that reveals the genetic contribution of CHRM3 gene in bladder cancer etiology.

Zhang N, Jiang G, Liu X, et al.
Prediction of Bacillus Calmette-Guerin Response in Patients with Bladder Cancer after Transurethral Resection of Bladder Tumor by Using Genetic Variation Based on Genomic Studies.
Biomed Res Int. 2016; 2016:9859021 [PubMed] Free Access to Full Article Related Publications
Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded. Results. The genetic variations associated with BCG response can be classified into three categories: germline variations, somatic variations, and epigenetic alterations. Genes related to BCG response were mainly involved in single-nucleotide polymorphisms, copy number variations, and gene methylations. Conclusions. Although these gene alterations are currently the most promising predictive markers of BCG response, most studies about bladder cancer DNA biomarkers are related to germline variations in candidate genes, and the results are not consistent. Only one study is related to somatic variation, and further evaluation in large-scale validation studies should be conducted to assess the potential clinical application of these findings. In addition, other biomarkers based on different "-omics" technologies should be considered in future studies.

Chen YJ, Wang HF, Liang M, et al.
Upregulation of miR-3658 in bladder cancer and tumor progression.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Despite increasing advances in surgical techniques and adjuvant chemotherapies, bladder cancer remains the ninth leading cause of male malignancy-associated deaths worldwide. Several microRNAs (miRNAs) have been identified to be closely associated with the progression and prognosis of, and response to treatments in various human cancers. However, few studies have investigated the role of miR-3658 in bladder cancer. In this study, we examined the expression of miR-3658 in 96 pairs of bladder cancer tissues and adjacent non-tumor tissues via quantitative reverse-transcription polymerase chain reaction. Results showed that expression of miR-3658 was up-regulated in the bladder cancer tissues as compared with that in the corresponding control tissues (4.15 ± 2.78 vs 2.17 ± 1.14; P < 0.0001). Furthermore, higher miR-3658 expression was significantly associated with lymph node invasion, distant metastasis, histological grade, TNM stage, and tumor recurrence in bladder cancer (all P < 0.0001). miR-3658 expression was not associated with other clinicopathological variables such as age, gender, tumor size, and number (all P > 0.05). Our study revealed that miR-3658 overexpression is involved in tumor progression of bladder cancer, indicating that the miRNA possesses prognostic values.

Anzivino E, Zingaropoli MA, Iannetta M, et al.
Archetype and Rearranged Non-coding Control Regions in Urothelial Bladder Carcinoma of Immunocompetent Individuals.
Cancer Genomics Proteomics. 2016 11-12; 13(6):499-509 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Polyomaviruses (PyVs) are potential transforming viruses. Despite their involvement in human tumours still being debated, there is evidence to suggest a role for PyVs in bladder carcinoma (BC). Therefore, a possible association between PyVs and BC was investigated.
MATERIALS AND METHODS: Urine, blood and fresh bladder tissue specimens were collected from 29 patients with BC. PyV prevalence, non-coding control region (NCCR) organization and genotypic analysis were assessed.
RESULTS: Data showed a significant prevalence of John Cunningham (JC) PyV in BC tissues and in urine with respect to BKPyV, while simian virus 40 was not revealed. A BKPyV rearranged NCCR sequence was isolated, whereas a JCPyV archetypal structure was consistently retained. A prevalence of European genotypes was observed.
CONCLUSION: Our data would suggest a JCPyV involvement in cancer progression and a BKPyV association with BC pathogenesis in immunocompetent patients. However, further work is necessary to better understand the exact role of PyVs in urothelial carcinogenesis.

Kriegmair MC, Balk M, Wirtz R, et al.
Expression of the p53 Inhibitors MDM2 and MDM4 as Outcome Predictor in Muscle-invasive Bladder Cancer.
Anticancer Res. 2016; 36(10):5205-5213 [PubMed] Related Publications
AIM: To evaluate the prognostic role of the p53-upstream inhibitors MDM2, MDM4 and its splice variant MDM4-S in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).
MATERIALS AND METHODS: mRNA Expression levels of MDM2, MDM4 and MDM4-S were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) in 75 RC samples. Logistic regression analyses identified predictors of recurrence-free (RFS) and cancer-specific survival (CSS).
RESULTS: High expression was found in 42% (MDM2), 27% (MDMD4) and 91% (MDM4-S) of tumor specimens. Increased MDM2 expression was significantly associated with higher tumor stage (p=0.05) and lymphovascular invasion (LVI) (p=0.041). In the univariate analysis, low MDM4 expression (hazard ratio (HR)=5.93; p=0.002; HR=3.00; p=0.047), but not MDM2 (HR=1.63; p=0.222; HR=1.59; p=0.27), were associated with RFS and CSS. In the multivariate analysis, the combination of low MDM4 and high MDM2 was significant for RFS and CSS (HR=14.9; p=0.001; HR=5.63; p=0.019).
CONCLUSION: The combination of MDM2 and MDM4 expression is an independent predictor in patients undergoing RC for MIBC.

Breyer J, Wirtz RM, Laible M, et al.
ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle-invasive bladder carcinoma (NMIBC).
Virchows Arch. 2016; 469(5):547-552 [PubMed] Related Publications
Pathological staging and grading are crucial for risk assessment in non-muscle-invasive bladder cancer (NMIBC). Molecular grading might support pathological evaluation and minimize interobserver variability. In this study, the well-established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as potential molecular markers to support grading and staging in NMIBC. We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the aforementioned markers was measured by single-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific TaqMan assays. Relative gene expression was determined by normalization to two reference genes (CALM2 and B2M) using the 40(-ΔΔCT) method and correlated to histopathological stage and grade. Pathological assessment was performed by an experienced uropathologist. Statistical analysis was performed using the SAS software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC, samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman rank correlation revealed significant correlations between grade and expression of MKI67 (r = 0.52, p < 0.0001), ESR1 (r = 0.25, p < 0.0001), and ERBB2 (r = 0.18, p = 0.0008). In Mann-Whitney tests, MKI67 was significantly different between all grades (p < 0.0001), while ESR1 (p = 0.0006) and ERBB2 (p = 0.027) were significantly different between G2 and G3. Higher expression of MKI67 (r = 0.49; p < 0.0001), ERBB2 (r = 0.22; p < 0.0001), and ESR1 (r = 0.18; p = 0.0009) mRNA was positively correlated with higher stage. MKI67 (p < 0.0001), ERBB2 (p = 0.0058), and PGR (p = 0.0007) were significantly different between pTa and pT1. In NMIBC expression of ESR1, ERBB2 and MKI67 are significantly different between stage and grade. This potentially provides objective parameters for pathological evaluation.

Wei Y, He R, Wu Y, et al.
Comprehensive investigation of aberrant microRNA profiling in bladder cancer tissues.
Tumour Biol. 2016; 37(9):12555-12569 [PubMed] Related Publications
There has been accumulative evidence that microRNAs (miRNAs) play essential roles in the tumorigenesis and progression of bladder cancer. However, individual studies and small sample size caused discrepant outcomes. Thus, the current study focused on a comprehensive profiling of all differentially expressed miRNAs in a total of 519 bladder cancer tissue samples, based on miRNA microarray data. Altogether, 11 prioritized miRNAs stated by 21 published microarray datasets, including five down-regulated (miR-133a-3p, miR-1-3p, miR-99a-5p, miR-490-5p, and miR-133b) and six up-regulated candidate miRNAs (miR-182-5p, miR-935, miR-518e-3p, miR-573, miR-100-3p, and miR-3171) were analyzed with vote-counting strategy and a Robust Rank Aggregation method. Subsequently, miRNA in silico target prediction and potential pathway enrichment analysis were performed to investigate the prospective molecular mechanism of miRNAs in the tumorigenesis of bladder cancer. We found that most of the relative pathways of the aberrantly expressed miRNAs found in the current study were closely correlated with different biological processes, cellular components, molecular functions, cancer pathogeneses, and some cell signalings, such as Wnt signaling, insulin/IGF, PI3 kinase, and FGF signaling pathways. Hence, a comprehensive overview on the miRNA expression pattern in bladder cancer tissues was gained by the current study. These miRNAs might be involved in the tumorigenesis and deterioration of bladder cancer.

Kumondai M, Hosono H, Orikasa K, et al.
CYP2A13 Genetic Polymorphisms in Relation to the Risk of Bladder Cancer in Japanese Smokers.
Biol Pharm Bull. 2016; 39(10):1683-1686 [PubMed] Related Publications
Tobacco-specific nitrosamines including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), which can be activated by the metabolic enzyme CYP2A13, are potent procarcinogens. Smoking plays a role in carcinogenesis in the human bladder, which expresses CYP2A13 at a relatively high level. Numerous genetic polymorphisms of CYP2A13 causing amino acid substitution might reduce CYP2A13 metabolic activity toward NNK and NNN, resulting in decreased susceptibility to bladder cancer. The aim of this study was to reveal any association between bladder cancer development and CYP2A13 genetic polymorphisms in Japanese smokers. The CYP2A13 genotype of each subject (163 bladder cancer patients and 161 controls) was determined by next-generation sequencing (NGS) of the full CYP2A13 gene. All samples were genotyped for five CYP2A13 variant alleles (CYP2A13*2, *3, *4, *6, *7). Based on biological logistic regression, the odds ratio (95% confidence interval) for the CYP2A13*1/*2 genotype was 0.34 (0.17-0.69). Thus, CYP2A13 genetic polymorphisms might play important roles in the development of bladder cancer in Japanese smokers.

Wang YY, Wu ZY, Wang GC, et al.
LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p.
Tumour Biol. 2016; 37(11):14553-14563 [PubMed] Related Publications
To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

Yu Y, Li X, Liang C, et al.
The relationship between GSTA1, GSTM1, GSTP1, and GSTT1 genetic polymorphisms and bladder cancer susceptibility: A meta-analysis.
Medicine (Baltimore). 2016; 95(37):e4900 [PubMed] Related Publications
BACKGROUND: Previous studies have investigated the relationship between GSTA1, GSTM1, GSTP1, and GSTT1 polymorphisms and bladder cancer (BCa) susceptibility, respectively, but the results remain inconsistent. So, we conducted this meta-analysis including 79 case-control studies to explore such relationships.
METHODS: We searched PubMed, EMBASE, Cochrane library, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were implemented to evaluate the intensity of associations. Publication bias was estimated using Begg funnel plots and Egger regression test. To assess the stability of the results, we used sensitivity analysis with the method of calculating the results again by omitting 1 single study each time. Between-study heterogeneity was tested using the I statistic.
RESULTS: No significant association between GSTA1 polymorphism and BCa susceptibility (OR = 1.05, 95% CI 0.83-1.33) was noted. Besides, meaningful association between individuals who carried the GSTM1 null genotype and increased BCa risk was detected (OR = 1.39, 95%CI 1.28-1.51). When stratified by ethnicity, significant difference was found in both Caucasian (OR = 1.39, 95% CI 1.23-1.58) and Asian populations (OR = 1.45, 95% CI 1.31-1.61). Moreover, in the subgroup analysis by source of controls (SOC), the results were significant in both hospital-based control groups (OR = 1.49, 95% CI 1.35-1.64) and population-based control groups (OR = 1.21, 95% CI = 1.07-1.37). Additionally, the analysis revealed no significant association between GSTP1 polymorphism and BCa risk (OR = 1.07, 95% CI 0.96-1.20). What is more, significant associations between GSTT1 polymorphism and BCa susceptibility were discovered (OR = 1.11, 95% CI 1.00-1.22). In the subgroup analysis by ethnicity, significant associations between GSTT1 null genotype and BCa risk were observed only in Caucasians (OR = 1.25, 95% CI 1.09-1.44). Furthermore, when stratified by SOC, no obvious relationship was found between the GSTT1 null genotype polymorphism with hospital-based population (OR = 1.11, 95% CI 0.97-1.28) or population-based population (OR = 1.10, 95% CI 0.96-1.27).
CONCLUSION: This study suggested that GSTM1 null genotype and GSTT1 null genotype might be related to higher BCa risk, respectively. However, no associations were observed between GSTA1 or GSTP1 polymorphisms and BCa susceptibility.

Chang WS, Liao CH, Tsai CW, et al.
Association of Enhancer of Zeste 2 (EZH2) Genotypes with Bladder Cancer Risk in Taiwan.
Anticancer Res. 2016; 36(9):4509-14 [PubMed] Related Publications
AIM: Bladder cancer is the sixth most common cancer worldwide and its incidence is particularly high in many developed regions including southwestern Taiwan. However, the genetic contribution to the etiology of bladder cancer is not well-understood. The aim of this study was to evaluate the association of the enhancer of zeste homolog 2 (EZH2) genotypes with Taiwan bladder cancer risk.
MATERIALS AND METHODS: Three polymorphic variants of EZH2 were analyzed regarding their association with bladder cancer risk, and three hundred and seventy-five patients with bladder cancer and same number of age- and gender-matched healthy controls recruited were genotyped by the PCR-RFLP method.
RESULTS: Among the three polymorphic sites examined, the genotypes of EZH2 rs887569 (C to T), but not rs41277434 (A to C) or rs3757441 (T to C), were positively associated with bladder cancer risk (p for trend =0.0146). Individuals with the EZH2 rs887569 TT genotypes were associated with decreased cancer risk than those with wild-type CC genotype. The stratified analyses showed that EZH2 rs887569 TT genotypes had protective effects on non-smokers but obviously not on smokers.
CONCLUSION: Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers.

Washio M, Mori M, Mikami K, et al.
Risk Factors for Upper and Lower Urinary Tract Cancer Death in a Japanese Population: Findings from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study).
Asian Pac J Cancer Prev. 2016; 17(7):3545-9 [PubMed] Related Publications
BACKGROUND: The incidence of bladder cancer is lower in Asian than in Western countries. However, the crude incidence and mortality of bladder cancer have recently increased in Japan because of the increased number of senior citizens. We have already reported risk factors for urothelial cancer in a large populationbased cohort study in Japan (JACC study). However, we did not evaluate the cancer risk in the upper and lower urinary tract separately in our previous study.
MATERIALS AND METHODS: Here we evaluated the risk of cancer death in the upper and lower urinary tracts, separately, using the database of the JACC study. The analytic cohort included 46,395 males and 64,190 females aged 40 to 79 years old. The Cox proportional hazard model was used to determine hazard ratios and their 95% confidence intervals.
RESULTS: Current smoking increased the risk of both upper and lower urinary tract cancer deaths. A history of kidney disease was associated with an increased risk of bladder cancer death, even after controlling for age, sex and smoking status.
CONCLUSIONS: The present study confirmed that current smoking increases the risk of both upper and lower urinary tract cancer deaths and indicated the possibility that a history of kidney disease may be a risk factor for bladder cancer death in the Japanese population.

Ma C, Gu L, Yang M, et al.
rs1495741 as a tag single nucleotide polymorphism of N-acetyltransferase 2 acetylator phenotype associates bladder cancer risk and interacts with smoking: A systematic review and meta-analysis.
Medicine (Baltimore). 2016; 95(31):e4417 [PubMed] Free Access to Full Article Related Publications
Rs1495741 has been identified to infer N-acetyltransferase 2 (NAT2) acetylator phenotype, and to decrease the risk of bladder cancer. However, a number of studies conducted in various regions showed controversial results. To quantify the association between rs1495741 and the risk of bladder cancer and to estimate the interaction effect of this genetic variant with smoking, we performed a systematic literature review and meta-analysis involving 14,815 cases and 58,282 controls from 29 studies. Our results indicates rs1495741 significantly associated with bladder cancer risk (OR = 0.85, 95% CI = 0.82-0.89, test for heterogeneity P = 0.36, I = 7.0%). And we verified this association in populations from Europe, America, and Asia. Further, our stratified meta-analysis showed rs1495741's role is typically evident only in ever smokers, which suggests its interaction with smoking. This study may provide new insight into gene-environment study on bladder cancer.

Ellinger J, Schneider AC, Bachmann A, et al.
Evaluation of Global Histone Acetylation Levels in Bladder Cancer Patients.
Anticancer Res. 2016; 36(8):3961-4 [PubMed] Related Publications
BACKGROUND/AIM: Alterations of global histone modification levels have been identified in various tumor entities, including bladder cancer (BCA). Our study was designed to investigate the value of global histone acetylation levels as diagnostic and prognostic biomarker for BCA patients.
MATERIALS AND METHODS: A tissue microarray with formalin-fixed paraffin-embedded tissues (271 BCA and 29 normal urothelial samples) was used to determine global histone acetylation levels (histone H3 acetylation (H3Ac); histone H3 lysine 18 acetylation (H3K18Ac); histone H4 acetylation (H4Ac)).
RESULTS: Global H3Ac levels were decreased in BCA patients, whereas H3K18Ac and H4Ac levels were similar in both groups. All studied histone acetylation markers were lower in muscle-invasive BCA compared to non-muscle invasive BCA and normal urothelial tissue, thereby indicating a possible prognostic relevance.
CONCLUSION: Global histone acetylation levels undergo quantitative alterations during bladder cancer progression and could be helpful to identify patients at risk for early cancer recurrence.

Wang M, Xiao X, Zeng F, et al.
Common and differentially expressed long noncoding RNAs for the characterization of high and low grade bladder cancer.
Gene. 2016; 592(1):78-85 [PubMed] Related Publications
Our study aimed to explore long non-coding RNAs (lncRNAs) contributing to the development of bladder cancer, as well as to identify more critical DEGs and lncRNAs that would characterize low- and high-grade bladder cancer. The microarray data of GSE55433 was downloaded from Gene Expression Omnibus database, including 57 urothelial cancer samples (23 low-grade NMI, 14 high-grade NMI and 20 invasive tumors) and 26 normal controls. The differentially expressed genes (DEGs) and differentially expressed lncRNAs were identified in 3 groups (low-grade NMI vs. normal, high-grade NMI vs. normal and invasive UC vs. normal). Functional enrichment analysis was performed upon the DEGs in different groups. Besides, protein-protein interaction (PPI) network was constructed based on common DEGs and remaining DEGs in each group. Co-expression analysis was performed to identify the co-expressed DEG-lncRNAs pairs. Different number of DEGs and differentially expressed lncRNAs were respectively identified from those 3 groups. NONHSAG013805 (down-regulated) and NONHSAG009271 (down-regulated) were common lncRNAs. NONHSAG013805 was connected with the down-regulated gene EIF3E and NONHSAG009271 was linked to MYL12A (down-regulated). Moreover, NONHSAG034203 (up-regulated) was co-expressed with ADM5 (up-regulated) in low-grade NMI cancer, while the down-regulated NONHSAG045391 was connected with the down-regulated DEGs DAD1 and STUB1 in high-grade NMI cancer and invasive bladder cancer. Our study indicates that NONHSAG013805 and NONHSAG009271 may play key roles in bladder cancer via co-expressing with EIF3E and MYL12A, respectively. Moreover, NONHSAG034203 may be involved in low-grade NMI bladder cancer via targeting ADM5, while NONHSAG045391 may contribute to high-grade NMI and invasive bladder cancer via targeting DAD1 and STUB1.

Zhu L, Zhou L, Wang L, et al.
A20 SNP rs77191406 may be related to secondary cancer for rheumatoid arthritis and systemic lupus erythematosus patients.
Asia Pac J Clin Oncol. 2016; 12(4):409-414 [PubMed] Related Publications
AIM: An increased risk for malignancy for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients may be related to factors that play a critical role in the regulation of T-cell activation. A20 is an important negative immunoregulatory factor that was found to be associated with lymphoma and the development of numerous solid tumors. Previous studies have implicated the A20 locus in RA susceptibility. In this study, we investigated polymorphisms in the A20 3' UTR and explored whether there was an association between these polymorphisms and malignancy risk in autoimmune diseases.
METHODS: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) from 99 RA cases, 37 SLE cases and 99 healthy individuals. Pearson's Chi square test was used for statistical analysis.
RESULTS: Only one SNP (rs77191406) and one new mutation (20132 A>G) in A20 gene were identified in RA and SLE patients and healthy individuals. Heterozygous rs77191406 was identified in just 1 of 99 RA patients and 2 of 37 SLE patients. More importantly, a RA patient who was heterozygous for rs77191406 developed colon cancer 10 years after the RA diagnosis. Similarly, two SLE patients carrying rs77191406 (heterozygous) had severe disease or developed bladder cancer 5 years after SLE diagnosis.
CONCLUSIONS: These findings suggest that rs77191406 may be a prognostic marker for a high risk for rapid malignancy progression, poor survival and refractory disease and a new molecular marker associated with autoimmune diseases transforming into a secondary cancer.

He A, Chen Z, Mei H, Liu Y
Decreased expression of LncRNA MIR31HG in human bladder cancer.
Cancer Biomark. 2016; 17(2):231-6 [PubMed] Related Publications
OBJECTIVE: In this study, we examined the relationships between the expression level of long non-coding RNA MIR31HG in bladder cancer and the clinical characteristics.
METHODS: A total of 55 tissue samples from patients with bladder cancer were collected, and the lncRNA MIR31HG levels in cancer, paired non-cancer tissues and BC cell lines were detected by real-time quantitative RT-PCR (qRT-PCR). The relationships between MIR31HG level and the clinical characteristics were evaluated.
RESULTS: MIR31HG expression was remarkably decreased in bladder cancer tissues compared with adjacent noncancerous tissues (P < 0.05). MIR31HG expression was also significantly down-regulated in four bladder cancer cell lines (P < 0.001). Clinicopathologic analysis revealed that MIR31HG expression was negatively associated with TNM stage (P = 0.010), but not with other clinicopathological characteristics.
CONCLUSIONS: These findings revealed that MIR31HG may function as a cancer-suppressor gene to participate in the bladder cancer carcinogenesis and development.

Zhang Y, Zhang Z, Li Z, et al.
MicroRNA-497 inhibits the proliferation, migration and invasion of human bladder transitional cell carcinoma cells by targeting E2F3.
Oncol Rep. 2016; 36(3):1293-300 [PubMed] Related Publications
Accumulating evidence indicates that microRNAs (miRNAs) play critical roles in regulating cellular processes, such as cell growth and apoptosis, as well as cancer progression and metastasis. Low expression of miR-497 has been observed in breast, colorectal and cervical cancers. Human bladder transitional cell carcinoma (BTCC) progression typically follows a complex cascade from primary malignancy to distant metastasis, but whether the aberrant expression of miR-497 in BTCC is associated with malignancy, metastasis or prognosis remains unknown. In the present study, we found that miR-497 was markedly downregulated in BTCC tissue samples when compared with that noted in adjacent normal tissues, and low expression of miR-497 was correlated with poor prognosis in BTCC patients. We also found that overexpression of miR-497 inhibited the proliferation, migration and invasion of bladder cancer cells by downregulating E2F3 (an miR-497 target gene) mRNA and protein and that siRNA against E2F3 inhibited cell proliferation, migration and invasion, which was similar to the effect of miR-497 overexpression in the BTCC cells. Our experimental data indicated that miR-497 mediates the in vitro proliferation, migration and invasion of BTCC cells. Together, these results suggest that miR-497 may represent a novel prognostic indicator, a biomarker for the early detection of metastasis and a target for gene therapy of BTCC.

Pandith AA, Hussain A, Khan MS, et al.
Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer.
Asian Pac J Cancer Prev. 2016; 17(6):2787-93 [PubMed] Related Publications
BACKGROUND: Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases.
MATERIALS AND METHODS: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing.
RESULTS: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3.
CONCLUSIONS: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

Yonemori M, Seki N, Yoshino H, et al.
Dual tumor-suppressors miR-139-5p and miR-139-3p targeting matrix metalloprotease 11 in bladder cancer.
Cancer Sci. 2016; 107(9):1233-42 [PubMed] Free Access to Full Article Related Publications
Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNA, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome-wide gene expression analysis, in silico analysis and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.

Zhang X, Zhang Y
Bladder Cancer and Genetic Mutations.
Cell Biochem Biophys. 2015; 73(1):65-9 [PubMed] Related Publications
The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder cancer need further research.

Zhang N, Bi X, Zeng Y, et al.
TGF-β1 promotes the migration and invasion of bladder carcinoma cells by increasing fascin1 expression.
Oncol Rep. 2016; 36(2):977-83 [PubMed] Related Publications
Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine that is reported to regulate cellular motility and invasive capability during tumor progression. Fascin1, an actin-bundling protein, increases cell motility, migration and adhesion. To investigate the function of TGF-β1 and test whether fascin1 is an important mediator of the tumor response to TGF-β1 in bladder carcinoma cells, real-time RT-PCR and western blot analysis were used to test changes in fascin1 expression after TGF-β1 (10 ng/ml) treatment in T24 and BIU87 cells. Small interfering RNA (siRNA) technique was performed to silence fascin1. Cell viability and biological behavior changes were evaluated by cell growth (MTT), wound-healing and Matrigel invasion assays. In the present study, we found that the mRNA and protein levels of fascin1 in the T24 and BIU87 cells were significantly increased after 10 ng/ml TGF-β1 treatment (p<0.05). The proliferation of T24 cells (p=0.005) was also significantly increased, while no significant change was observed in BIU87 cells (p=0.318). In addition, the migratory and invasive potential of the two cell lines were promoted. Furthermore, we successfully silenced fascin1, and observed that fascin1 siRNA significantly attenuated the migration and invasiveness induced by TGF-β1. The findings suggested that TGF-β1 can promote invasion and migration of T24 and BIU87 bladder carcinoma cells, and the increase in fascin1 expression may be the key point of this impact of TGF-β1.

Kouba E, Cheng L
Neuroendocrine Tumors of the Urinary Bladder According to the 2016 World Health Organization Classification: Molecular and Clinical Characteristics.
Endocr Pathol. 2016; 27(3):188-99 [PubMed] Related Publications
Neuroendocrine neoplasms of the urinary bladder are a rare type of tumor that account for a small percentage of urinary bladder neoplasms. These tumors of the urinary bladder range from well-differentiated neuroendocrine neoplasms (carcinoids) to the more aggressive subtypes such as small cell carcinoma. Despite the rarity of the neuroendocrine tumors of the bladder, there has been substantial investigation into the underlying genomic, molecular, and the cellular alterations within this group of neoplasms. Accordingly, these findings are increasingly incorporated into the understanding of clinical aspects of these neoplasms. In this review, we provide an overview of recent literature related to the 2016 World Health Organization Classification of Neuroendocrine Tumors of the Urinary Bladder. Particular emphasis is placed on molecular alterations and recently described gene expression. The neuroendocrine tumors of the urinary bladder are subdivided into four subtypes. Similar to their pulmonary and other extrapulmonary site counterparts, these have different degrees of neuroendocrine differentiation and morphological features. The clinical aspects of four subtypes of neuroendocrine tumor are discussed with emphasis of the most recent developments in diagnosis, treatment, and prognosis. An understanding of molecular basis of neuroendocrine tumors will provide a base of knowledge for future investigations into this group of unusual bladder neoplasms.

Song YL, Wang L, Ren JC, Xu ZH
CYP1A2-163C/A (rs762551) polymorphism and bladder cancer risk: a case-control study.
Genet Mol Res. 2016; 15(2) [PubMed] Related Publications
To date, no study has investigated the association between CYP1A2-163C/A polymorphism and bladder cancer risk in a Chinese population. Here, we extracted genomic DNA from peripheral white blood cells, and differentiated CYP1A2 alleles by polymerase chain reaction-based restriction fragment length polymorphism methods. Differences in genotype frequencies between the cases and controls were evaluated using a chi-square test. The odds ratio (OR) and its 95% confidence interval (CI) were calculated using an unconditional logistic regression model. This revealed that the -163A allele was present at a significantly increased frequency in bladder cancer patients compared to healthy controls (44.10 vs 22.25%, P < 0.001). The prevalence of CC genotype, CA genotype, and AA genotype was 34.91, 41.98, and 23.11% in bladder cancer patients, and 64.00, 27.50, and 8.5% in the controls, respectively. Therefore, significant differences in the frequencies of -163 genotypes were found between bladder cancer patients and controls (P < 0.001). We found that the AA genotype was significantly associated with increased bladder cancer risk (OR = 3.72; 95%CI = 1.55-7.16; P = 0.02), and the -163A carriers were at increased risk of bladder cancer in a multivariate COX regression model (OR = 4.89, 95%CI = 2.78-10.87, P = 0.01). We conclude that the CYP1A2-163C/A polymorphism is associated with increased susceptibility to bladder cancer in the Chinese population.

Zhang M, Zhuang Q, Cui L
MiR-194 inhibits cell proliferation and invasion via repression of RAP2B in bladder cancer.
Biomed Pharmacother. 2016; 80:268-75 [PubMed] Related Publications
Bladder cancer is the 7th most common cancer type in the world, and microRNAs (miRNAs) play important roles in cancer progression. In the present study, we investigated the roles and molecular mechanisms of miR-194 in bladder cancer. The results demonstrated that the expression level of miR-194 is significantly down-regulated in bladder cancer cell lines and clinical tissues. Overexpression of miR-194 inhibited cell proliferation and invasion in J82 and T24 cells. Further mechanistic study showed that overexpression of miR1-94 induced G0/G1 phase arrest as well as apoptosis in J82 and T24 cells. In addition, by using bioinformatics tool (Targetscan), RAP2B is found to be a target of miR-194, and miR-194 down-regulates the expression level of RAP2B via directly targeting its 3'UTR. Knockdown of RAP2B also inhibited cell proliferation and invasion in J28 cells. More importantly, restoration of RAP2B activity rescued the inhibitory effects of miR-194 on cell proliferation and invasion in J82 cells. Further analysis of bladder cancer clinical samples showed that miR-194 is inversely correlated with RAP2B. Collectively, our study may implicate that miR-194 plays an important role in the regulation of bladder cancer progression. In summary, our study may implicate that miR-194 acts as a tumor suppressor and plays an important role in the regulation of bladder cancer progression.

Ding XL, Yang X, Liang G, Wang K
Isoform switching and exon skipping induced by the DNA methylation inhibitor 5-Aza-2'-deoxycytidine.
Sci Rep. 2016; 6:24545 [PubMed] Free Access to Full Article Related Publications
DNA methylation in gene promoters leads to gene silencing and is the therapeutic target of methylation inhibitors such as 5-Aza-2'-deoxycytidine (5-Aza-CdR). By analyzing the time series RNA-seq data (days 5, 9, 13, 17) obtained from human bladder cells exposed to 5-Aza-CdR with 0.1 uM concentration, we showed that 5-Aza-CdR can affect isoform switching and differential exon usage (i.e., exon-skipping), in addition to its effects on gene expression. We identified more than 2,000 genes with significant expression changes after 5-Aza-CdR treatment. Interestingly, 29 exon-skipping events induced by treatment were identified and validated experimentally. Particularly, exon-skipping event in Enhancer of Zeste Homologue 2 (EZH2) along with expression changes showed significant down regulation on Day 5 and Day 9 but returned to normal level on Day 13 and Day 17. EZH2 is a component of the multi-subunit polycomb repressive complex PRC2, and the down-regulation of exon-skipping event may lead to the regain of functional EZH2 which was consistent with our previous finding that demethylation may cause regain of PRC2 in demethylated regions. In summary, our study identified pervasive transcriptome changes of bladder cancer cells after treatment with 5-Aza-CdR, and provided valuable insights into the therapeutic effects of 5-Aza-CdR in current clinical trials.

Tiryakioglu NO, Tunali NE
Association of AKR1C3 Polymorphisms with Bladder Cancer.
Urol J. 2016; 13(2):2615-21 [PubMed] Related Publications
PURPOSE: Polymorphisms in the genes coding for the carcinogen metabolizing enzymes may affect enzyme activities and alter the activation and detoxification rates of the carcinogens. AKR1C3 is one of the very polymorphic xenobiotic metabolizing enzymes involved in the bioactivation process. Here we aimed to investigate the association of two single nucleotide polymorphisms in AKR1C3, rs12529 (c.15C > G) and rs1937920 (12259 bp 3' of STP A > G) with urinary bladder cancer (UBC).
MATERIALS AND METHODS: Two-hundred fifty UBC cases and 250 control subjects were genotyped using the Polymerase Chain Reaction and Restriction Fragment Length method. Associations of the genotypes with UBC risk and tumor characteristics were assessed using logistic regression and Fisher's exact test. The results are corrected for multiple testing.
RESULTS: We identified strong associations between the studied AKR1C3 variants and UBC risk. The homozygous variant genotype of rs12529 was found to be inversely associated with UBC, and rs1937920 was shown to be associated with increased risk of UBC. None of the genotypes were found to be significantly associated with tumor characteristics.
CONCLUSION: We provided evidence that rs12529 and rs1937920 are significant in the molecular pathogenesis of UBC. However, the results presented here should be regarded as preliminary and might represent a first step of future larger studies aiming to better elucidate the role of AKR1C3 polymorphisms in the susceptibility to bladder cancer.

Recurrent Chromosome 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.

Chromosome Y Loss in Bladder Cancer

Khaled HM, Aly MS, Magrath IT
Loss of Y chromosome in bilharzial bladder cancer.
Cancer Genet Cytogenet. 2000; 117(1):32-6 [PubMed] Related Publications
Bilharzial bladder cancer is the most common malignant neoplasm in Egypt, also occurring with a high incidence in other regions of the Middle East and East Africa. In a previous study, using centromere probes specific for chromosomes 3, 4, 7-11, 16, and 17, we demonstrated that monosomy of chromosome 9 (48.4%), and numerical aberrations of chromosome 17 (19.4%) were the most common observed imbalances. The present study extends the establishment of the baseline cytogenetic profile of this type of malignancy. Interphase cytogenetics by fluorescence in situ hybridization with the use of a panel of centromere-associated DNA probes for chromosomes 1, 2, 5, 6, 12, 13/21, 14, 15, 18, 19, 20, X, and Y was performed on paraffin-embedded bladder specimens from 25 Egyptian patients affected with bilharzial bladder cancer. No numerical aberrations were detected in the 25 cases for chromosomes 1, 2, 5, 6, 12, 13/21, 14, 15, 18, 19, 20, and X. However, loss of chromosome Y was observed in 7 of the 17 male cases studied (41.2%). No significant correlation was observed between loss of the Y chromosome and any of the different clinicopathologic characteristics of these cases. These data suggest that loss of the Y chromosome is the second frequent event that can occur in bilharzial bladder cancer. A molecular genetic model of bilharzial bladder cancer is evolving.

Sauter G, Moch H, Wagner U, et al.
Y chromosome loss detected by FISH in bladder cancer.
Cancer Genet Cytogenet. 1995; 82(2):163-9 [PubMed] Related Publications
To examine the significance of Y chromosome losses in bladder cancer, fluorescence in situ hybridization (FISH) was used to determine its prevalence and associations with known parameters of malignancy. Cells were dissociated from formalin-fixed paraffin-embedded bladder tumors from 68 male patients and from 11 post-mortem bladder washes of male patients with a negative bladder cancer history, and were examined by FISH using centromeric probes for chromosomes X, Y, 7, 9, and 17. Nullisomy for chromosome Y was seen in 23 of 68 tumors (34%), monosomy in 28 of 68 tumors (41%), and polysomy in 17 of 68 tumors (25%). There was no association between chromosome Y loss and tumor grade, stage, tumor growth fraction (Ki67 LI), p53 immunostaining, and presence of p53 deletions. Patient age was higher for tumors with a Y loss (73.5 +/- 12.0 years) than for tumors without Y loss (66.6 +/- 10.8 years; p = 0.0207). In one normal bladder wash, a distinct subpopulation (38% of cells) with Y nullisomy was seen. These data suggest that Y loss is a frequent event that can occur early in bladder cancer, although there is no evidence for a role of Y loss in tumor progression.

del(9q) in Bladder Cancer

Loss of heterozygosity (LOH) on chromosome arm 9 is the most frequent genetic alteration in transitional cell carcinomas. Candidate tumor suppressor genes/loci have been proposed, including: CDKN2 and DBCCR1.

Habuchi T, Yoshida O, Knowles MA
A novel candidate tumour suppressor locus at 9q32-33 in bladder cancer: localization of the candidate region within a single 840 kb YAC.
Hum Mol Genet. 1997; 6(6):913-9 [PubMed] Related Publications
Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder, implicating the presence of a tumour suppressor gene or genes on 9q. To define the location of a tumour suppressor locus on 9q in TCC, we screened 156 TCCs of the bladder and upper urinary tract by detailed deletion mapping using 31 microsatellite markers on 9q. Partial deletions of 9q were found in 10 TCCs (6%), and LOH at all informative loci on 9q was found in 77 TCCs (49%). In five low grade superficial bladder tumours, the partial deletion was localized to D9S195 located at 9q32-33, with retention of heterozygosity at all other informative loci including D9S103, D9S258, D9S275 and GSN. We constructed a yeast artificial chromosome (YAC) contig covering the deleted region in these five tumours and placed another four unmapped microsatellite markers on this contig map. Using these markers, we further defined the common deleted region to the interval between D9S1848 and AFMA239XA9. The region is covered by a single YAC (852e11), whose size is estimated to be 840 kb. Our data should expedite further fine mapping and identification of the candidate tumour suppressor gene at 9q32-33.

Habuchi T, Luscombe M, Elder PA, Knowles MA
Structure and methylation-based silencing of a gene (DBCCR1) within a candidate bladder cancer tumor suppressor region at 9q32-q33.
Genomics. 1998; 48(3):277-88 [PubMed] Related Publications
Loss of heterozygosity (LOH) on chromosome 9q is the most frequent genetic alteration in transitional cell carcinoma (TCC) of the bladder, indicating the presence of one or more relevant tumor suppressor genes. We previously mapped one of these putative tumor suppressor loci to 9q32-q33 and localized the candidate region within a single YAC 840 kb in size. This locus has been designated DBC1 (for deleted in bladder cancer gene 1). We have identified a novel gene, DBCCR1, in this candidate region by searching for expressed sequence tags (ESTs) that map to YACs spanning the region. Database searching using the entire DBCCR1 cDNA sequence identified several human ESTs and a few homologous mouse. ESTs. However, the predicted 761-amino-acid sequence had no significant homology to known protein sequences. Mutation analysis of the coding region and Southern blot analysis detected neither somatic mutations nor gross genetic alterations in primary TCCs. Although DBCCR1 was expressed in multiple normal human tissues including urothelium, mRNA expression was absent in 5 of 10 (50%) bladder cancer cell lines. Methylation analysis of the CpG island at the 5' region of the gene and the induction of de novo expression by a demethylating agent indicated that this island might be a frequent target for hypermethylation and that hypermethylation-based silencing of the gene occurs in TCC. These findings make DBCCR1 a good candidate for DBC1.

Knowles MA
Identification of novel bladder tumour suppressor genes.
Electrophoresis. 1999; 20(2):269-79 [PubMed] Related Publications
Many genetic alterations have recently been identified in transitional cell carcinoma (TCC) of the bladder. These include alterations to known proto-oncogenes and tumour suppressor genes and the identification of multiple sites of nonrandom chromosomal deletion which are predicted to define the location of as yet unidentified tumour suppressor genes. This review summarises recent efforts to define the location of novel bladder tumour suppressor genes using loss of heterozygositiy (LOH) and homozygous deletion analyses and to isolate the genes targeted by these deletions. For three of the four regions of deletion on chromosome 9, the most frequently deleted chromosome in TCC, candidate genes have been identified. It is anticipated that the identification of the genes and/or genetic regions which are frequently altered in TCC will provide useful tools for diagnosis, prediction of prognosis, patient monitoring and novel therapies.

van Tilborg AA, Groenfeld LE, van der Kwast TH, Zwarthoff EC
Evidence for two candidate tumour suppressor loci on chromosome 9q in transitional cell carcinoma (TCC) of the bladder but no homozygous deletions in bladder tumour cell lines.
Br J Cancer. 1999; 80(3-4):489-94 [PubMed] Free Access to Full Article Related Publications
The most frequent genetic alterations in transitional cell carcinoma (TCC) of the bladder involve loss of heterozygosity (LOH) on chromosome 9p and 9q. The LOH on chromosome 9p most likely targets the CDKN2 locus, which is inactivated in about 50% of TCCs. Candidate genes that are the target for LOH on chromosome 9q have yet to be identified. To narrow the localization of one or more putative tumour suppressor genes on this chromosome that play a role in TCC of the bladder, we examined 59 tumours with a panel of microsatellite markers along the chromosome. LOH was observed in 26 (44%) tumours. We present evidence for two different loci on the long arm of chromosome 9 where potential tumour suppressor genes are expected. These loci are delineated by interstitial deletions in two bladder tumours. Our results confirm the results of others and contribute to a further reduction of the size of these regions, which we called TCC1 and TCC2. These regions were examined for homozygous deletions with EST and STS markers. No homozygous deletions were observed in 17 different bladder tumour cell lines.

Simoneau M, Aboulkassim TO, LaRue H, et al.
Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31.
Oncogene. 1999; 18(1):157-63 [PubMed] Related Publications
The most common genetic alteration identified in transitional cell carcinoma (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9. However, localization of tumor suppressor genes on 9q has been hampered by the low frequency of subchromosomal deletions. We have analysed 139 primary, initial low stage TCC of the bladder using a panel of 28 microsatellite markers spanning chromosome 9 at an average distance of 5 Mb, following a primer-extension preamplification (PEP) technique. Sixty-seven (48%) tumors showed LOH at one or more loci and partial deletions were detected in 62 (45%) tumors; apparent monosomy 9 was detected in only five (4%) tumors. Deletions were more frequent on 9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion, suggesting that alteration of genes on 9q may be an early event associated with superficial papillary tumors. Combined data from the cases with partial 9q deletions displayed four candidate regions for tumor suppressor loci, based on the frequency of deletion observed and tumors with unique deletions at these sites. In two tumors, the unique partial deletion comprised D9S12 at 9q22.3, a region encompassing loci for the Gorlin syndrome and multiple self-healing squamous epithelioma gene. In two other tumors, the single LOH was identified at the D9S172 locus at 9q31-32 where the dysautonia and Fukuyama-type congenital muscular dystrophy genes have been located. One tumor showed unique LOH at the GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the fourth region of deletion was observed at 9q34 between ASS and ABL-1, in two tumors. This region is frequently deleted in tumors and encompasses the locus for the hereditary hemorrhagic telangiectasia gene. These findings suggest four target regions on 9q within which suppressor genes for TCC may reside.

Uroplakins and Bladder Cancer

Uroplakins are membrane proteins specific to mammalian urothelium. These are expressed in both normal and cancerous urothelium. Mutations have rarely been reported, however, uroplakins act as a useful marker for detecting metastases and circulating TCC cells. The uroplakin family includes: UKP1A, UKP1B, UKP2 and UKP3.
Moll R, Wu XR, Lin JH, Sun TT
Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas.
Am J Pathol. 1995; 147(5):1383-97 [PubMed] Free Access to Full Article Related Publications
Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin.

Wu RL, Osman I, Wu XR, et al.
Uroplakin II gene is expressed in transitional cell carcinoma but not in bilharzial bladder squamous cell carcinoma: alternative pathways of bladder epithelial differentiation and tumor formation.
Cancer Res. 1998; 58(6):1291-7 [PubMed] Related Publications
Uroplakins (UPs) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-II gene and localized it on chromosome 11q23. A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36) of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.

Yuasa T, Yoshiki T, Tanaka T, et al.
Expression of uroplakin Ib and uroplakin III genes in tissues and peripheral blood of patients with transitional cell carcinoma.
Jpn J Cancer Res. 1998; 89(9):879-82 [PubMed] Related Publications
Uroplakins (UPs), urothelium-specific transmembrane proteins, are present only in urothelial cells. We have determined the nucleotide sequences of human UP-Ib and UP-III and synthesized specific primer pairs. The two UP genes were expressed in both cancerous and noncancerous urothelial taken from all patients examined by reverse transcription-polymerase chain reaction (RT-PCR). These genes were also detected in the peripheral blood of 3 patients with metastatic transitional cell carcinoma (TCC), but not in that from 9 patients with non-metastatic TCC or 3 healthy volunteers. The sensitivity of our assay was sufficient to detect one cancer cell in 5 ml of peripheral blood. Detection of UP gene-expression in blood by RT-PCR may provide helpful information for the diagnosis and management of TCC.

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

Cite this page: Cotterill SJ. Bladder Cancer - Molecular Biology, Cancer Genetics Web: http://www.cancer-genetics.org/X2103.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