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DDX1; DEAD (Asp-Glu-Ala-Asp) box helicase 1 (2p24)

Gene Summary

Gene:DDX1; DEAD (Asp-Glu-Ala-Asp) box helicase 1
Aliases: DBP-RB, UKVH5d
Location:2p24
Summary:DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein of unknown function. It shows high transcription levels in 2 retinoblastoma cell lines and in tissues of neuroectodermal origin. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:ATP-dependent RNA helicase DDX1
HPRD
Source:NCBI
Updated:14 December, 2014

Gene
Ontology:

What does this gene/protein do?
Show (29)

Cancer Overview

Research Indicators

Publications Per Year (1989-2014)
Graph generated 14 December 2014 using data from PubMed using criteria.

Literature Analysis

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

  • Cancer DNA
  • Adolescents
  • Gene Dosage
  • Oligonucleotide Array Sequence Analysis
  • Cancer Gene Expression Regulation
  • Molecular Sequence Data
  • Genetic Predisposition
  • Proto-Oncogene Proteins c-myc
  • Neuroblastoma
  • Retinoblastoma
  • Survival Rate
  • Messenger RNA
  • Nuclear Proteins
  • DEAD-box RNA Helicases
  • Base Sequence
  • Chromosome Mapping
  • Cancer RNA
  • Tumor Virus Infections
  • Virus Replication
  • Oncogene Proteins
  • Transcriptional Activation
  • Polymerase Chain Reaction
  • Newborns
  • Rhabdomyosarcoma, Alveolar
  • RNA Nucleotidyltransferases
  • Up-Regulation
  • Chromosome 2
  • myc Genes
  • RTPCR
  • DDX1
  • Infant
  • RNA Helicases
  • Turkey
  • DNA, Complementary
  • Tumor Markers
  • Gene Amplification
  • FISH
  • Childhood Cancer
  • Neoplasm Proteins
  • Staging
Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (2)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
NeuroblastomaDDX1 Amplification in Neuroblastoma View Publications22
RetinoblastomaDDX1 Amplification in Retinoblastoma cell lines View Publications3

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

Related Links

Latest Publications: DDX1 (cancer-related)

Johanneson B, Chen D, Enroth S, et al.
Systematic validation of hypothesis-driven candidate genes for cervical cancer in a genome-wide association study.
Carcinogenesis. 2014; 35(9):2084-8 [PubMed] Related Publications
A large number of genetic associations with cervical cancer have been reported in hypothesis-driven candidate gene studies, but most studies have not included an independent replication or the results have been inconsistent between studies. In order to independently validate these associations, we reexamined 58 candidate gene/regions previously reported to be associated with cervical cancer using the gene-based Adaptive Rank Truncated Product test in a genome-wide association study (GWAS) of 1034 cervical cancer patients and 3948 controls from the Swedish population. Of the 58 gene/regions, 8 had a nominal P value < 0.05 [tumor necrosis factor (TNF), P = 5.0 × 10(-4); DEAD (Asp-Glu-Ala-Asp) box helicase 1 [DDX1], P = 2.2 × 10(-3); exonuclease 1 [EXO1], P = 4.7 × 10(-3); excision repair cross-complementing rodent repair deficiency, complementation group 1 [ERCC1], P = 0.020; transmembrane channel-like 6 and 8 genes [TMC6-TMC8], P = 0.023; secreted phosphoprotein 1 [SPP1], P = 0.028; v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 [ERBB2], P = 0.033 and chloride channel, voltage-sensitive 7 [CLCN7], P = 0.047). After correction for multiple testing, only TNF remained statistically significant (P = 0.028). Two single-nucleotide polymorphisms that are in nearly perfect linkage disequilibrium (rs2857602 and rs2844484) contributed most to the association with TNF. However, they are not independent from the previously reported associations within the MHC region. The very low number of previously reported associations with cervical cancer that replicate in the Swedish population underscore the need to apply more stringent criteria when reporting associations, including the prerequisite of replicating the association as part of the original study.

Related: Cervical Cancer


Fievet A, Belaud-Rotureau MA, Dugay F, et al.
Involvement of germline DDX1-MYCN duplication in inherited nephroblastoma.
Eur J Med Genet. 2013; 56(12):643-7 [PubMed] Related Publications
This report concerns a 3-year-old girl with prenatal bilateral nephroblastomatosis and a family history of nephroblastoma. This girl had a chromosome 8 pericentric inversion inherited from her father. This inversion was observed in healthy individuals of the family and was absent in other individuals suffering from embryonic kidney tumor. We then supposed that another genetic anomaly predisposed her to tumorogenesis. Additional cryptic imbalances are reported in cases of apparently balanced chromosomal rearrangements with an abnormal phenotype. Array-CGH analysis showed a 569 kb duplication at 2p24.3 including the DDX1 and MYCN genes. This duplication was inherited from the patient's father who also had a nephroblastoma. A link between germline MYCN duplication and the occurrence of other embryonic cancers such as neuroblastoma has already been described. We supposed that germline DDX1-MYCN duplication could also be involved in the apparition of nephroblastomas.

Related: Chromosome 8 CGH Kidney Cancer Wilms' Tumour Wilms Tumour MYCN (n-myc)


Bagci O, Tumer S, Olgun N, Altungoz O
Copy number status and mutation analyses of anaplastic lymphoma kinase (ALK) gene in 90 sporadic neuroblastoma tumors.
Cancer Lett. 2012; 317(1):72-7 [PubMed] Related Publications
Somatic and germline mutations of the anaplastic lymphoma kinase (ALK) gene were recently described in neuroblastoma (NB). In this study, we investigated the association of ALK copy number alterations with copy number status 2p24.1 amplicon harboring DEAD box polypeptide 1 (DDX1), MYCN and neuroblastoma-amplified (NAG) genes in 90 primary tumors of sporadic NB cases by multiplex ligation-dependent probe amplification (MLPA). We also performed mutation analysis of ALK gene by directly sequencing the exons 20-28 which cover the region that encodes juxtamembrane and kinase domains. A total of 39 (43.3%) NB cases revealed copy numbers alterations of ALK gene. There was highly significant association of ALK copy number gains with gains of one or more of the genes at 2p24.1 (DDX1, MYCN or NAG) in MYCN unamplified tumors (P<0.000). In addition, 15 of 17 MYCN amplified cases (88.2%) had aberrant ALK status. Solitary gain of ALK with normal copy number status of all other genes was observed only in one case. DNA sequencing of exons 20-28 of ALK revealed two different nucleotide changes in three cases leading to amino acid substitutions of F1245V and R1275Q in tyrosine kinase domain. In conclusion, the frequency of ALK mutations in NB is low and solitary copy number change of it is rarely observed.

Related: Neuroblastoma MYCN (n-myc)


Taunk NK, Goyal S, Wu H, et al.
DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node-negative breast cancer.
Cancer. 2012; 118(4):888-98 [PubMed] Related Publications
BACKGROUND: DEAD box 1 (DDX1) is an RNA helicase with a number of roles, including translation initiation, RNA splicing and modification, and possibly DNA double-strand break repair. Amplification of DDX1 expression has been implicated in tumors including neuroblastoma, Wilms tumor, retinoblastoma, and testicular carcinoma. The purpose of this study was to evaluate the prognostic significance of DDX1 expression in patients with breast cancer treated with breast-conserving therapy.
METHODS: Paraffin-embedded specimens from 282 women with node-negative stage 1 and 2 breast cancer treated with breast-conserving surgery and radiation therapy were constructed into tissue microarrays and stained for DDX1. The molecular profiles were correlated with clinicopathologic factors and overall, local, and distant metastatic-free survival.
RESULTS: DDX1 positivity was identified in 142 (50%) patients. The median age at diagnosis was 53 years. Eighty percent of the patients had T1 disease; 11% were HER2neu-positive, and 18% had triple-negative disease. DDX1 negativity was strongly associated with triple-negative phenotype (P = .01). DDX1 positivity was found to be associated with improved local relapse-free survival (96% vs 85%, P = .0233), distant metastatic-free survival (95% vs 85%, P = .0320), and overall survival (92% vs 84%, P = .0474) at 10 years.
CONCLUSIONS: Node-negative, early stage breast cancer patients with high levels of DDX1 were found to have a significant improvement in local control, distant metastatic-free survival, and overall survival compared with patients with low levels of DDX1.

Related: Breast Cancer


de Souza DR, Sanabani SS, de Souza AC, et al.
Prognostic impact of MYCN, DDX1, TrkA, and TrkC gene transcripts expression in neuroblastoma.
Pediatr Blood Cancer. 2011; 56(5):749-56 [PubMed] Related Publications
BACKGROUND: The aims of this study were to define the mRNA expression profiles of MYCN, DDX1, TrkA, and TrkC in biopsy tumor samples from 64 Brazilian patients with neuroblastomas of different risk stages and to correlate altered expression with prognostic values.
PROCEDURE: Patients were retrospectively classified into low- (n = 11), intermediate- (n = 18), and high-risk (n = 35) groups using standard criteria. The mRNA levels of the above genes were measured by quantitative real-time polymerase chain reaction. Univariate analyses were performed and survival curves were plotted by the Kaplan-Meier method.
RESULTS: Of the 64 patients, 53% were female and 62.5% were older than 18 months. The 5-year overall survival (OS) for the entire cohort was 40.3%, with inferior median OS in patients identified in the intermediate- and high-risk groups. A significant difference in OS with respect to TrkA mRNA expression was found for the high-risk group vs. either the low- or intermediate-risk groups (P < 0.01, log rank test). Within the intermediate-risk group, neuroblastoma patients with positive TrkA mRNA expression had better clinical outcomes than patients with no TrkA transcript expression (P = 0.004). Another difference in OS was only found between the intermediate- and high-risk groups (P < 0.027, log rank test). No significant correlation of mRNA expression and survival outcome could be detected for the MYCN, DDX1.
CONCLUSIONS: Positive expression of TrkA mRNA may be a clinically useful addition to the current risk classification system, allowing the identification of NB tumors with favorable prognosis.

Related: Neuroblastoma NTRK1 gene NTRK3 gene MYCN (n-myc)


Germain DR, Graham K, Glubrecht DD, et al.
DEAD box 1: a novel and independent prognostic marker for early recurrence in breast cancer.
Breast Cancer Res Treat. 2011; 127(1):53-63 [PubMed] Related Publications
Breast cancer is a heterogeneous disease characterized by diverse molecular signatures and a variable response to therapy. Clinical management of breast cancer is guided by the expression of estrogen and progesterone receptors and HER2 amplification. New prognostic and predictive markers, as well as additional targets for therapy, are needed for more effective management of this disease. Gene expression microarrays were probed with RNAs from 176 primary breast cancer samples and tissue microarrays immunostained with anti-DDX1 antibody, an antibody to DEAD box protein DDX1, a putative RNA-RNA and RNA-DNA unwinding protein normally found in the nucleus. Half of the patient cohort had experienced early relapse despite standard adjuvant therapy, but were otherwise matched for estrogen receptor and HER2 status, stage and duration of follow-up. Here, we identify DDX1 RNA overexpression as an independent prognostic marker for early recurrence in primary breast cancer, with a hazard ratio of 4.31 based on logrank analysis of Kaplan-Meier curves. Elevated levels of DDX1 protein in the cytoplasm also independently correlate with early recurrence with a hazard ratio of 1.90. In conclusion, our data indicate a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1. We propose that elevated levels of DDX1 RNA or the presence of DDX1 in the cytoplasm could serve as an effective prognostic biomarker for early recurrence in primary breast cancer.

Related: Breast Cancer


Noguera R, Villamón E, Berbegall A, et al.
Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line.
Diagn Mol Pathol. 2010; 19(1):33-9 [PubMed] Related Publications
Wilms tumor is one of the most common pediatric malignant tumors of the kidney. Although the WT1 gene, located at 11p13, has been proven to be implicated in the development of Wilms tumor, other genes such as MYCN are also involved. The purpose of this study is to genetically characterize a Wilms tumor metastasis xenotransplanted in nude mice. Immunogenotype evolution of the xenografts material was monitored for 29 months using molecular techniques, fluorescent in situ hybridization and multiplex ligation-dependent probe amplification, in addition to immunohistochemistry in tissue microarrays. Genetic alterations present in the original tumor and retained in the xenotransplanted tumor were located in +1q, +3, +6, -7p, +7q, +8, -9p, +9q, +12. The multiplex ligation-dependent probe amplification detected a nondeleted status of genes located close to WT genes, except for a deletion of the EGFR gene (located at 7p11.2) and the GHRHR gene (located at 7p15), both flanking the WT5 gene. The MYCN gene (2p24 exon 3) and DDX1 gene (2p24 exons 2, 7, 15, and 24) were gained in passage 4 and the following passages. MYCN expression was positive from the beginning, without evidence of MYCN gain by fluorescent in situ hybridization. Histopathologic and growth rate changes were observed at those passages where low extra copy number of MYCN was present. In addition to other genetic abnormalities, the WT5 gene located at 7p13-14 is deleted and the MYCN gene gain began after 16 months in vivo evolution in athymic nude mice. MYCN is already used as a stratifying marker in neuroblastomas, and it may be also useful in implementing MYCN testing in prospective studies of Wilms tumors.

Related: FISH Wilms' Tumour Wilms Tumour MYCN (n-myc)


Barr FG, Duan F, Smith LM, et al.
Genomic and clinical analyses of 2p24 and 12q13-q14 amplification in alveolar rhabdomyosarcoma: a report from the Children's Oncology Group.
Genes Chromosomes Cancer. 2009; 48(8):661-72 [PubMed] Free Access to Full Article Related Publications
Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer that is related to the skeletal muscle lineage and characterized by recurrent chromosomal translocations. Within the ARMS category, there is clinical and genetic heterogeneity, consistent with the premise that "primary" genetic events collaborate with "secondary" events to give rise to subsets with varying clinical features. Previous studies demonstrated that genomic amplification occurs frequently in ARMS. In the current study, we used oligonucleotide arrays to localize two common amplicons to the 2p24 and 12q13-q14 chromosomal regions. Based on the copy number array data, we sublocalized the minimum common regions of 2p24 and 12q13-q14 amplification to a 0.83 Mb region containing the DDX1 and MYCN genes, and a 0.55 Mb region containing 27 genes, respectively. Using fluorescent in situ hybridization assays to measure copy number of the 2p24 and 12q13-q14 regions in over 100 cases, we detected these amplicons in 13% and 12% of cases, respectively. Comparison with fusion status revealed that 2p24 amplification occurred preferentially in cases positive for PAX3-FOXO1 or PAX7-FOXO1 while 12q13-q14 amplification occurred preferentially in PAX3-FOXO1-positive cases. Expression studies demonstrated that MYCN was usually overexpressed in cases with 2p24 amplification while multiple genes were overexpressed in cases with 12q13-q14 amplification. Finally, although 2p24 amplification did not have a significant association with clinical outcome, 12q13-q14 amplification was associated with significantly worse failure-free and overall survival that was independent of gene fusion status.

Related: Chromosome 12 Chromosome 2 CDK4 FISH PAX7 gene FOXO1A gene MYCN (n-myc) PAX3 gene


Tanaka K, Okamoto S, Ishikawa Y, et al.
DDX1 is required for testicular tumorigenesis, partially through the transcriptional activation of 12p stem cell genes.
Oncogene. 2009; 28(21):2142-51 [PubMed] Related Publications
Cytogenetic analysis has identified 12p gain as the most frequent abnormality in human testicular germ cell tumors (TGCTs). It has been suggested that amplification and overexpression of stem cell-associated genes, including cyclin-D2, on the human chromosome 12p region are involved in germ cell tumorigenesis. By subtractive cDNA analysis, we identified Ddx1, a member of the DEAD-box protein family, as a gene predominantly expressed in the primordial germ cells of mouse embryos. Knockdown of Ddx1 in a mouse spermatogonia-derived cell line, GC-1spg, by short interference RNA repressed the expression of cyclin-D2, CD9 and GDF3 genes. In the mouse cyclin-D2 gene, a genomic DNA region between -348 and -329 was responsible for transcriptional activation by DDX1 based on reporter and gel shift assays. Similarly, DDX1 knockdown in the human TGCT cell line NEC8 repressed the expression of stem cell-associated genes localized on chromosome 12p13.3, including cyclin-D2, CD9 and NANOG. DDX1-knocked-down TGCT cells could not form solid tumors in nude mice. Furthermore, in situ hybridization revealed that DDX1 mRNA was produced in both seminoma and nonseminoma types of human TGCT samples. We conclude that DDX1 is a critical factor for testicular tumorigenesis.

Related: Chromosome 12 Testicular Cancer


Hodgson JG, Yeh RF, Ray A, et al.
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts.
Neuro Oncol. 2009; 11(5):477-87 [PubMed] Free Access to Full Article Related Publications
Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors, genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.


Godbout R, Li L, Liu RZ, Roy K
Role of DEAD box 1 in retinoblastoma and neuroblastoma.
Future Oncol. 2007; 3(5):575-87 [PubMed] Related Publications
Analysis of hereditary and nonhereditary retinoblastoma led to the formulation of the two-hit hypothesis of cancer in the early 1970s. The two-hit hypothesis was validated in the 1980s when both copies of the RB1 gene were shown to be mutated in hereditary and nonhereditary retinoblastoma. However, consistent genetic abnormalities other than RB1 mutations suggest that additional events may be required for the formation of these malignant tumors. For example, MYCN amplification has long been known to occur in both retinoblastoma and neuroblastoma tumors and is strongly associated with poor prognosis in neuroblastoma. The DEAD box gene, DEAD box 1 (DDX1), is often coamplified with MYCN in both these childhood tumors. Here, we examine possible roles for DDX1 overexpression in retinoblastoma and neuroblastoma.

Related: Neuroblastoma Retinoblastoma


Defferrari R, Tonini GP, Conte M, et al.
Concomitant DDX1 and MYCN gain in neuroblastoma.
Cancer Lett. 2007; 256(1):56-63 [PubMed] Related Publications
DDX1, a gene mapping to the 2p24 region, has been observed to be co-amplified with MYCN in neuroblastoma. Co-amplification of the DDX1 gene is a consequence of the short physical distance between the two genes. Recently, it has been found that neuroblastoma cells can show a low increase in MYCN gene copy number, defined as MYCN gain. We studied 13 neuroblastomas with MYCN gain to evaluate the status of the DDX1 gene. We investigated DDX1/MYCN gain by double-colour FISH on interphase nuclei. All cases showed concomitant low extra copy number of DDX1 and MYCN. Heterogeneous distribution of nuclei displaying DDX1/MYCN gain was observed in almost all tumours, suggesting a clonal evolution of cells with DDX1/MYCN gain. This is the first report that shows DDX1 co-gained with MYCN in neuroblastoma and indicates that DDX1 over-representation is closely associated with an increase in MYCN copy number in neuroblastoma cells. Since DDX1 has already been found co-amplified with MYCN, DDX1 gain seems to be a further rearrangement due to the physical proximity of the two genes. Moreover, all patients with DDX1/MYCN gain show a good overall survival but a high frequency of adverse events.

Related: FISH Neuroblastoma MYCN (n-myc)


Sunden Y, Semba S, Suzuki T, et al.
DDX1 promotes proliferation of the JC virus through transactivation of its promoter.
Microbiol Immunol. 2007; 51(3):339-47 [PubMed] Related Publications
Recently, we demonstrated that the DEAD box protein 1 (DDX1), an RNA helicase, and the cleavage stimulation factor (CstF) form a complex that binds to the JC virus transcriptional control region (JCV-TCR). Here, we examined the function of DDX1, which is expressed at much higher levels in the JCV-susceptible cell line IMR-32 than in non-susceptible cell lines. DDX1 had no effect on the replication efficiency of JCV, but overexpression of DDX1 significantly increased transactivation of the JCV promoter. Furthermore, DDX1 enhanced the expression of JCV proteins in JCV infected cells, and knockdown of DDX1 using small interfering (si) RNA suppressed the expression of JCV proteins. Our results clearly demonstrate that DDX1 regulates proliferation of JCV in vitro through transcriptional activation.


Sunden Y, Semba S, Suzuki T, et al.
Identification of DDX1 as a JC virus transcriptional control region-binding protein.
Microbiol Immunol. 2007; 51(3):327-37 [PubMed] Related Publications
To investigate the mechanism behind JC virus (JCV) cell specificity we performed electrophoretic mobility shift assays (EMSA) using probes derived from the JCV transcriptional control region (JCV-TCR). Using nuclear extracts from the JCV-susceptible neuroblastoma cell line IMR-32, EMSA revealed a 670 kDa JCV-TCR-binding protein complex designated as #3-bp. This complex could not be detected in nuclear extracts from non-susceptible cell lines. Using column chromatographic purifi-cation and microsequencing, we identified cleavage stimulation factor (CstF) as a component of #3-bp. However, as CstF is present in many cell types, we speculated that the IMR-32-specific component(s) of #3-bp bind CstF. We performed a yeast two-hybrid assay using CstF-77 as the bait against a HeLa cDNA-subtracted IMR-32 cDNA library. This analysis detected binding between CstF-77 and the RNA helicase DDX1. Subsequently, biotinylated DNA affinity precipitation and chromatin immunoprecipitation assays also confirmed that DDX1 binds specifically to JCV-TCR. Our findings indicate that an association between DDX1 and the JCV-TCR may play a significant role in JCV infection in IMR-32 cells.

Related: Neuroblastoma


Lo KC, Rossi MR, Burkhardt T, et al.
Overlay analysis of the oligonucleotide array gene expression profiles and copy number abnormalities as determined by array comparative genomic hybridization in medulloblastomas.
Genes Chromosomes Cancer. 2007; 46(1):53-66 [PubMed] Related Publications
Combined analysis of gene expression array data and array-based comparative genomic hybridization data have been used in a series of 26 pediatric brain tumors to define up- and downregulated genes that coincide with losses, gains, and amplifications involving specific chromosome regions. Frequent losses were defined in chromosome arms 3q, 6q, 8p, 10q, 16q, 17p, and gains were identified in chromosome 7, and chromosome arms 9p and 17q. Amplification of a 2p region was seen in only one tumor, which corresponded to increased expression of the MYCN and DDX1 genes. To facilitate the analysis of the two data sets, we have developed a custom overlay tool that defines genes that are underexpressed in regions of deletions and overexpressed in regions of gain, across the genome and specifically within regions showing recurrent involvement in medulloblastomas.

Related: Childhood Medulloblastoma / PNET


Kaneko S, Ohira M, Nakamura Y, et al.
Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma.
J Cancer Res Clin Oncol. 2007; 133(3):185-92 [PubMed] Related Publications
PURPOSE: Amplification of the MYCN gene strongly correlates with advanced stage, rapid tumor progression and poor prognosis in neuroblastoma (NB). Several genes in the MYCN amplicon, including the DEAD box polypeptide 1 (DDX1) gene, and neuroblastoma-amplified gene (NAG gene), have been found to be frequently co-amplified with MYCN in NB. The aim of this study was to clarify the prognostic significance of the co-amplification or overexpression of DDX1 and NAG with MYCN.
PROCEDURE: The gene copy numbers and mRNA expression levels of MYCN, DDX1, and NAG in 113 primary NBs were determined by the real-time quantitative polymerase chain reaction or quantitative reverse transcriptase/polymerase chain reaction assay. The relationships between gene co-amplification/overexpression status and stage, age at diagnosis, and overall survival were analyzed.
RESULTS: For evaluating the frequency of DDX1 and NAG co-amplification, it proved appropriate to discriminate NBs with <40 copies of MYCN amplification from those with > or =40 copies of MYCN (DDX1, p = 0.00058; NAG, p = 0.0242, chi(2) for independence test). In patients with MYCN-amplified NB aged > or =18 months, those with tumor with enhanced DDX1 expression and low-NAG expression showed a significantly better outcome than those with low-DDX1 expression or enhanced NAG expression (p = 0.0245, log-rank test). None of the gene expression statuses had a significant relation to disease stage or survival for patients <18 months old. No relationship between any gene co-amplification status and disease stage, age at diagnosis, or overall survival was found.
CONCLUSIONS: Our findings suggest that there may be a subset of NB in which enhanced DDX1 and low-NAG expression consequent to DDX1 co-amplification without NAG amplification contributes to susceptibility to intensive therapy. A larger study using an age cut-off of 18 months will be required.

Related: Neuroblastoma


Abdelhaleem M
Do human RNA helicases have a role in cancer?
Biochim Biophys Acta. 2004; 1704(1):37-46 [PubMed] Related Publications
Human RNA helicases (HRH) represent a large family of enzymes that play important roles in RNA processing. The biochemical characteristics and biological functions of the majority of HRH are still to be determined. However, there are examples of dysregulation of HRH expression in various types of cancer. In addition, some HRH have been shown to be involved in the regulation of, or the molecular interaction with, molecules implicated in cancer. Other helicases take part in fusion transcripts resulting from cancer-associated chromosomal translocation. These findings raise the question of whether HRH can contribute to cancer development/progression. In this review, I summarize the cancer-related features of HRH.

Related: Cancer Prevention and Risk Reduction DDX6 gene


Weber A, Imisch P, Bergmann E, Christiansen H
Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma.
J Clin Oncol. 2004; 22(13):2681-90 [PubMed] Related Publications
PURPOSE: Amplification of the MYCN oncogene at chromosome 2p24-25 identifies an aggressive subtype of human neuroblastoma with a poor clinical outcome. Differences in amplicon structure and coamplification of genes telomeric and centromeric to the MYCN oncogene have previously been described. A relevant role of gene coamplification for neuroblastoma pathogenesis remains elusive.
PATIENTS AND METHODS: We analyzed 98 primary neuroblastoma tumors with MYCN amplification for coamplification of seven additional genes at chromosome 2p24-25 (DDX1, NAG, NSE1, LPIN1, EST-AA581763, SMC6, and SDC1). Two semiquantitative multiplex polymerase chain reactions were used to obtain the amplification status of the target genes in relation to a reference gene on chromosome 2q (Inhibin-beta-b). Furthermore, mRNA expression pattern of coamplified genes in a subset of tumors was analyzed.
RESULTS: Our results show that the frequency of gene coamplification on 2p24-25 in neuroblastoma is correlated directly to the physical distance to MYCN. Coamplification is correlated to an upregulated gene expression for DDX1 and NAG. Coamplification of the DDX1 gene within 400kb telomeric to MYCN identifies a subgroup of advanced stage neuroblastoma tumors with a more favorable outcome (P =.027, log-rank test). A high expression level of DDX1 is associated with a trend towards a better survival probability (P =.058, log-rank test).
CONCLUSION: Our results indicate that DDX1 coamplification correlates with a better prognosis and improved patient survival in MYCN-amplified neurobastoma.

Related: Chromosome 2 Neuroblastoma MYCN (n-myc)


Scott D, Elsden J, Pearson A, Lunec J
Genes co-amplified with MYCN in neuroblastoma: silent passengers or co-determinants of phenotype?
Cancer Lett. 2003; 197(1-2):81-6 [PubMed] Related Publications
Amplification of the MYCN oncogene in neuroblastoma is associated with poor prognosis. The amplified unit of DNA can be up to 1 Mb in size and so could contain additional genes that affect tumour phenotype. Identification of such genes may assist in optimising the determination of prognosis, and could provide new targets for treatment. Three genes have so far been identified, which are frequently co-amplified with MYCN in neuroblastoma, DDX1, NAG and N-cym. In this review, the known or putative properties of the protein products of the genes are discussed, and their possible roles in determining tumour behaviour are assessed.

Related: Neuroblastoma


Scott DK, Board JR, Lu X, et al.
The neuroblastoma amplified gene, NAG: genomic structure and characterisation of the 7.3 kb transcript predominantly expressed in neuroblastoma.
Gene. 2003; 307:1-11 [PubMed] Related Publications
Amplification of the MYCN oncogene in neuroblastoma is associated with poor prognosis. The amplified unit of DNA can be up to 1 Mb in size and so could contain additional genes which affect tumour phenotype. The neuroblastoma amplified gene (NAG) gene was initially located 400 kb telomeric to MYCN at 2p24 and reported to be co-amplified in 5/8 (63%) cell lines and 9/13 (70%) tumours. The sequence of a 4.5 kb transcript was proposed from the analysis of overlapping cDNA clones. However, our Northern blot hybridisation experiments indicate that the main RNA species expressed in neuroblastoma is 7-8 kb in size. We describe for the first time the cloning and sequencing of the 7.3 kb transcript of the NAG gene together with its precise genomic location and full exon structure. The 5' end of the gene is located 30 kb telomeric to DDX1, with the two genes lying in opposite orientations. The 52 exons of the 7.3 kb transcript cover 420 kb of genomic DNA. In vitro translation studies confirmed the protein coding potential of the transcript. Co-amplification of the entire NAG gene with MYCN was found in 1/6 (17%) neuroblastoma cell lines and 10/50 (20%) primary tumours. Previous studies had measured co-amplification of only the 5' end of the gene, nearest to MYCN. In this study, co-amplification of the NAG gene was found to be significantly associated with low disease stage in MYCN-amplified tumours (P=0.0063).

Related: Neuroblastoma MYCN (n-myc)


Fischer M, Berthold F
Characterization of the gene expression profile of neuroblastoma cell line IMR-5 using serial analysis of gene expression.
Cancer Lett. 2003; 190(1):79-87 [PubMed] Related Publications
The serial analysis of gene expression (SAGE) technique was used to generate a database of the most abundant transcripts of the MYCN-amplified neuroblastoma cell line IMR-5. A total of 8568 tags were sequenced and shown to represent 4034 unique tags, each of which corresponds to an individual transcript. Expression levels of genes are reflected by the frequency of occurrence of the respective tags. To validate fidelity of SAGE data, relative abundances of seven transcripts were evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Transcripts that were detected nine times or more (>0.1% of the total tag population) accounted for 36% of the total messenger RNA mass but only 3% of the total number of individual transcripts. A strong preponderance of genes involved in protein synthesis, in particular those encoding for ribosomal proteins, were observed among these high-abundance transcripts. Tags corresponding to the amplified gene DDX1 were conspicuously overrepresented in comparison to the other amplified genes MYCN, neuroblastoma amplified gene and MEIS1, which suggests an additional mechanism apart from genomic amplification contributing to the strong upregulation of this gene. This study provides a comprehensive gene expression profile of neuroblastoma cell line IMR-5 and may be used as a reference database for identification of candidate genes that are involved in etiology and pathogenesis of neuroblastoma.

Related: Neuroblastoma


De Preter K, Speleman F, Combaret V, et al.
Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay.
Mod Pathol. 2002; 15(2):159-66 [PubMed] Related Publications
Amplification of the proto-oncogene MYCN is a strong adverse prognostic factor in neuroblastoma patients in all tumor stages. The status of the MYCN gene has become an important factor in clinical decision making and therapy stratification. Consequently, fast and accurate assessment of MYCN gene copy number is of the utmost importance and the use of two independent methods to determine MYCN status is recommended. For these reasons we have developed and evaluated a real-time quantitative PCR (Q-PCR) assay as an alternative for time-consuming Southern blot analysis (SB), and as a second independent technique in parallel with fluorescence in situ hybridization (FISH) analysis. Advantages of Q-PCR are a large dynamic range of quantification, no requirement for post-PCR sample handling and the need for very small amounts of starting material. The accuracy of the assay was illustrated by measurement of MYCN single gene copy changes in DNA samples of two patients with 2p deletion and duplication, respectively. Two different detection chemistries i.e., a sequence specific TaqMan probe and a generic DNA binding dye SYBR Green I were evaluated and shown to yield similar results. Also, two different calculation methods for copy number determination were used i.e., the kinetic method and the comparative C(T) method, and shown to be equivalent. In total, 175 neuroblastoma samples with known MYCN status, as determined by FISH and/or SB, were examined. Q-PCR data were highly concordant with FISH and SB data. In addition to MYCN copy number evaluation, DDX1 and NAG gene copy numbers were determined using a similar Q-PCR strategy. Survival analysis pointed out that DDX1 and/or NAG amplification has no additional adverse effect on prognosis.

Related: FISH Neuroblastoma


Wimmer K, Zhu XX, Lamb BJ, et al.
Two-dimensional DNA electrophoresis identifies novel CpG islands frequently coamplified with MYCN in neuroblastoma.
Med Pediatr Oncol. 2001; 36(1):75-9 [PubMed] Related Publications
BACKGROUND: Amplification of the oncogene MYCN in neuroblastoma has been found to correlate with aggressive tumour growth and is used as a predictor of clinical outcome. The MYCN amplicon is known to involve coamplification of extensive DNA regions. Therefore it is possible that other genes are coamplified in this amplicon and that they may play a role in the poor outcome of MYCN amplified tumours.
PROCEDURE: We have implemented an approach for the two-dimensional separation of human genomic restriction fragments to detect and isolate as yet unknown amplified sequences in the MYCN amplicon in neuroblastoma. Using this approach we have recently cloned a novel gene referred to as NAG that is frequently coamplified with MYCN in neuroblastoma.
RESULTS AND CONCLUSIONS: We report here the identification and cloning of two additional CpG islands that are amplified in neuroblastoma. One contains a sequence that is identical to the first intron of DDX1. The other represents a novel CpG island that is associated with an as yet unidentified gene. We show that the novel CpG island is located in close proximity to the MYCN locus on chromosome 2 and is as frequently coamplified with MYCN in neuroblastoma as NAG and DDX1.

Related: Chromosome 1 FISH Neuroblastoma


Pandita A, Zielenska M, Thorner P, et al.
Application of comparative genomic hybridization, spectral karyotyping, and microarray analysis in the identification of subtype-specific patterns of genomic changes in rhabdomyosarcoma.
Neoplasia. 1999; 1(3):262-75 [PubMed] Free Access to Full Article Related Publications
Rhabdomyosarcoma (RMS) in children occurs predominantly as two major histologically defined subtypes called embryonal RMS (RMS-E) and the prognostically less favorable alveolar RMS (RMS-A). Comparative genomic hybridization (CGH) was performed on 21 RMS and identified consistent gains affecting chromosomes 2 (8/10), 5 (5/10), 6 (3/10), 7 (7/10), 8 (9/10), 11 (6/ 10), and 12 (5/10) in RMS-E. Losses/deletions involved chromosomes 19 (2/10) and chromosomes 4, 9, 10, 17, 21 (1/10 each). High copy number amplification, involving the 2p24 region (5/11) and less frequently, the 12q13-21 (2/11), 9p22 (1/11), and 17q22-25 (1/11) regions, was detected in RMS-A. Gene amplification at band 2p24 was present in 6/12 alveolar tumors, and in each case, MYCN was amplified, together with the distally placed DDX1 gene. For these patients there was a shorter disease free interval and a higher mortality than patients with tumors without amplification. Detailed spectral karyotype analysis (SKY) was performed on two RMS cell lines (one of each subtype) and identified a surprisingly high level of structural change. Gene expression studies with the Atlas Human Cancer Array (588 genes) showed that 153 genes generated a signal of similar intensity in both cell lines, and 45 genes appeared to have subtype-specific expression. The chromosomal location of differentially expressed genes was compared to the pattern of genomic alteration in RMS as determined by CGH in this study and the literature.

Related: Rhabdomyosarcoma


Frühwald MC, O'Dorisio MS, Rush LJ, et al.
Gene amplification in PNETs/medulloblastomas: mapping of a novel amplified gene within the MYCN amplicon.
J Med Genet. 2000; 37(7):501-9 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: The pathological entity of primitive neuroectodermal tumour/medulloblastoma (PNET/MB) comprises a very heterogeneous group of neoplasms on a clinical as well as on a molecular level. We evaluated the importance of DNA amplification in medulloblastomas and other primitive neuroectodermal tumours (PNETs) of the CNS.
METHOD: Restriction landmark genomic scanning (RLGS), a method that allows the detection of low level amplification, was used. RLGS provides direct access to DNA sequences circumventing positional cloning efforts. Furthermore, we analysed several samples by CGH.
DESIGN: Twenty primary medulloblastomas, five supratentorial PNETs, and five medulloblastoma cell lines were studied.
RESULTS: Although our analysis confirms that gene amplification is generally a rare event in childhood PNET/MB, we found a total of 17 DNA fragments that were amplified in seven different tumours. Cloning and sequencing of several of these fragments confirmed the previous finding of MYC amplification in the cell line D341 Med and identified novel DNA sequences amplified in PNET/MB. We describe for the first time amplification of the novel gene, NAG, in a subset of PNET/MB. Despite genomic amplification, NAG was not overexpressed in the tumours studied. We have determined that NAG maps less than 50 kb 5' of DDX1 and approximately 400 kb telomeric of MYCN on chromosome 2p24.
CONCLUSION: We found a similar but slightly higher frequency of amplification than previously reported. We present several DNA fragments that may belong to the CpG islands of novel genes amplified in a small subset of PNET/MB. As an example we describe for the first time the amplification of NAG in the MYCN amplicon in PNET/MB.

Related: Childhood Brain Tumours Childhood Brain Tumors Childhood Medulloblastoma / PNET Polymorphisms


Akiyama K, Akao Y, Yokoyama M, et al.
Expression of two dead box genes (DDX1 and DDX6) is independent of that of MYCN in human neuroblastoma cell lines.
Biochem Mol Biol Int. 1999; 47(4):563-8 [PubMed] Related Publications
To examine whether two DEAD box genes, DDX1 and DDX6, would have some roles in the progression of tumors, we investigated the correlation of the expression of these genes with that of MYCN in neuroblastomas either with or without MYCN amplification. The mRNA of MYCN was observed only in the cell lines with amplification of MYCN. The mRNAs of DDX1 and DDX6 were found in all the cell lines examined, but the correlation between the mRNA levels of DDX1 or DDX6 and MYCN was poor. These findings suggest that the expression of neither DEAD box gene is correlated with the gene expression of MYCN.

Related: Neuroblastoma DDX6 gene


Godbout R, Packer M, Bie W
Overexpression of a DEAD box protein (DDX1) in neuroblastoma and retinoblastoma cell lines.
J Biol Chem. 1998; 273(33):21161-8 [PubMed] Related Publications
The DEAD box gene, DDX1, is a putative RNA helicase that is co-amplified with MYCN in a subset of retinoblastoma (RB) and neuroblastoma (NB) tumors and cell lines. Although gene amplification usually involves hundreds to thousands of kilobase pairs of DNA, a number of studies suggest that co-amplified genes are only overexpressed if they provide a selective advantage to the cells in which they are amplified. Here, we further characterize DDX1 by identifying its putative transcription and translation initiation sites. We analyze DDX1 protein levels in MYCN/DDX1-amplified NB and RB cell lines using polyclonal antibodies specific to DDX1 and show that there is a good correlation with DDX1 gene copy number, DDX1 transcript levels, and DDX1 protein levels in all cell lines studied. DDX1 protein is found in both the nucleus and cytoplasm of DDX1-amplified lines but is localized primarily to the nucleus of nonamplified cells. Our results indicate that DDX1 may be involved in either the formation or progression of a subset of NB and RB tumors and suggest that DDX1 normally plays a role in the metabolism of RNAs located in the nucleus of the cell.

Related: Neuroblastoma Retinoblastoma


George RE, Kenyon R, McGuckin AG, et al.
Analysis of candidate gene co-amplification with MYCN in neuroblastoma.
Eur J Cancer. 1997; 33(12):2037-42 [PubMed] Related Publications
Previous studies have revealed that the MYCN gene spans approximately 7kb, while the amplicon has been estimated to be 100 kb to 1 Mb long [1-3]. This implies that several other genes may be present on the MYCN amplicon. Such co-amplified genes could contribute to the malignant phenotype and might provide an explanation for why not all patients with MYCN amplification have a poor outcome. We investigated 7 neuroblastoma cell lines and 167 primary tumours for the co-amplification of candidate genes known to be present near the MYCN locus: ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box protein gene, DDX1. We also investigated further the pG21 expressed sequence previously reported to be co-amplified with MYCN. No co-amplification with the first 3 genes was found in any of the cell lines or tumour samples. DDX1 was found to be amplified along with MYCN in 4/6 (67%) cell lines and 18/38 (47%) of the MYCN amplified tumours. No amplification of DDX1, ODC1, RRM2 or syndecan-1 was found in the absence of MYCN amplification. DDX1 co-amplification was observed to occur mainly in stage 4 or 4S patients. With the exclusion of those with 4S disease, patients with DDX1 co-amplification had a significantly shorter mean (+/- SE) disease-free interval (4.1 +/- 1.4, n = 8 months) compared with patients with MYCN amplification alone (19.6 +/- 4.5, n = 17) (P = 0.04, Welch's unpaired t-test). The pG21 sequence was identical to part of the DDX1 gene. These observations indicate that there is at least 1 other gene co-amplified with MYCN in a proportion of cases and that those patients with DDX1 co-amplification tend to relapse more quickly. It also implies that the MYCN amplicon is of varied size and/or position relative to the MYCN gene.

Related: Neuroblastoma


Kuroda H, White PS, Sulman EP, et al.
Physical mapping of the DDX1 gene to 340 kb 5' of MYCN.
Oncogene. 1996; 13(7):1561-5 [PubMed] Related Publications
One of the most important prognostic factors in neuroblastoma is amplification of the MYCN gene, which is strongly associated with advanced stages of disease and a poor prognosis. Although the MYCN amplicon sometimes spans more than 1 Mb, no other consistently expressed sequences from the MYCN amplicon have been reported. However, DDX1, a gene encoding a DEAD box protein, was recently mapped to chromosome 2p24 and is frequently co-amplified with MYCN. Therefore, we performed genomic mapping with YACs to determine the physical relationship between DDX1 and MYCN, and whether DDX1 was contained within the core region of amplification. Based on YAC restriction mapping and content analysis, DDX1 maps 340 kb 5' of MYCN, outside the core domain of consistent amplification. Interestingly, we also determined by sequence analysis and detailed restriction mapping that G21, previously isolated as a 'neuroblastoma-specific' cDNA clone from an MYCN amplicon, is a partial cDNA of DDX1. Our data confirm that DDX1 is amplified in some but not all MYCN-amplified tumors, and that it is rearranged in other cases. This suggests that the co-amplification of DDX1 is due to its proximity to MYCN.

Related: Chromosome 2 Neuroblastoma


George RE, Kenyon RM, McGuckin AG, et al.
Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group.
Oncogene. 1996; 12(7):1583-7 [PubMed] Related Publications
Although N-myc amplification is strongly associated with a poor prognosis, not all patients with neuroblastomas having N-myc amplification fare badly. To investigate whether genes other than N-myc are responsible for contributing to the prognosis, we examined seven cell lines and 87 primary tumours for co-amplification of candidate genes known to be present near the normal N-myc locus: ornithine decarboxylase (ODC), ribonucleotide reductase (RRM2), syndecan-1 and a DEAD box protein gene, DDX1. Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene. No co-amplification with the first three genes was found in any of the cell lines or tumour samples. DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours. Co-amplification of DDX1 and N-myc was found more frequently in stage 4 or 4S tumours than lower stage (1-3) tumours. With the exclusion of a single 4S case, there was a highly significant reduction in the mean disease-free interval from 24.4 +/- 4.7 (SE, n = 10) months for cases with co-amplification of N-myc and DDX1 compared with 9.2 +/- 1.8 (SE, n = 5) months for those cases showing amplification of N-myc alone (P = 0.0056, Welch's unpaired t-test). No amplification of DDX1, ODC, RRM2, or syndecan-1 was found in the absence of N-myc amplification. These observation indicate that the N-myc amplicon is of varied size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene frequently co-amplified with N-myc. Further studies are required to confirm the biological and prognostic significance of DDX1 co-amplification and to elucidate the role that DDX1 plays in tumour genesis and progression.

Related: Neuroblastoma SDC1


Squire JA, Thorner PS, Weitzman S, et al.
Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma.
Oncogene. 1995; 10(7):1417-22 [PubMed] Related Publications
DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing. These proteins share eight conserved amino acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more extended motif. Recently, we have shown that the novel DDX1 gene containing a DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co-amplified with MYCN in retinoblastoma cell lines. Here, we show that the DDX1 gene is co-amplified with the MYCN gene in 2 of three neuroblastoma cell lines and that DDX1 RNA levels correlate with DDX1 gene copy number. Since amplification of MYCN is an indicator of poor prognosis in neuroblastoma, it was of interest to determine whether co-amplification with DDX1 occurred in clinical samples of neuroblastoma and whether such a finding carried any additional prognostic significance. We determined the gene copy number of DDX1 in 32 neuroblastoma patient samples (representative of all stages): 13 were MYCN amplified and 19 had normal copy numbers of the MYCN gene. Of the 13 neuroblastomas that were MYCN amplified, seven were also DDX1 amplified. Of the 19 that were not MYCN amplified, none were DDX1 amplified. This is the first example of a gene that is co-amplified with MYCN at a high frequency in neuroblastoma. While there was a trend towards a worse clinical outcome with co-amplification, the numbers were too small to reach significance.

Related: Neuroblastoma


Godbout R, Hale M, Bisgrove D
A human DEAD box protein with partial homology to heterogeneous nuclear ribonucleoprotein U.
Gene. 1994; 138(1-2):243-5 [PubMed] Related Publications
In a previous report, we showed that a novel DEAD box protein-encoding gene, DDX1, was amplified in two retinoblastoma (RB) cell lines. In addition to the eight conserved motifs that characterize all DEAD box proteins, the deduced amino acid sequence of DDX1 contains a subregion with considerable homology to heterogeneous nuclear ribonucleoprotein U.

Related: Eye Cancer Retinoblastoma


Godbout R, Squire J
Amplification of a DEAD box protein gene in retinoblastoma cell lines.
Proc Natl Acad Sci U S A. 1993; 90(16):7578-82 [PubMed] Free Access to Full Article Related Publications
DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp, are putative RNA helicases implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Here, we report that the mRNA encoding a DEAD box protein, designated HuDBP-RB, is present at elevated levels in two of six retinoblastoma (RB) cell lines tested and is preferentially expressed in fetal tissues of neuroectodermal origin. It is not possible to classify HuDBP-RB as a member of any of the DEAD box protein subgroups identified to date since the regions of amino acid similarity between HuDBP-RB and other DEAD box proteins are restricted to the conserved motifs found in all members of this family. The HuDBP-RB gene, which has been mapped to chromosome band 2p24, is amplified in the RB cell lines that overexpress HuDBP-RB RNA. Furthermore, the MYCN gene is also present in multiple copies in these two cell lines, suggesting coamplification of the two genes.

Related: Chromosome 2 Eye Cancer FISH Cancer Prevention and Risk Reduction Retinoblastoma


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