The DDX1 gene maps within 400 kbp 5′ to MYCN and is frequently coamplified in human neuroblastoma

Amler, Lukas C.; Schürmann, Jörg; Schwab, Manfred

doi:10.1002/(sici)1098-2264(199602)15:2<134::aid-gcc9>3.3.co;2-x

Cited by 10 publications

(19 citation statements)

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“…However, it is also possible that more than one gene can exist as a tumor-specific gene in the same amplicon. For example, PDGFRA has been found to be co-amplified with KIT , along with the vascular endothelial growth factor receptor gene KDR , at 4q12, and DDX1 and N-Myc are co-amplified at 2p24 (33). The co-amplification of multiple genes within a genomic region may have synergistic effects on neoplastic pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma Proto-oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress

Zhou

Killela

et al. 2009

Cancer Research

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Glioblastoma multiforme is the most prevalent type of adult brain tumor and one of the deadliest tumors known to mankind. The genetic understanding of glioblastoma multiforme is, however, limited, and the molecular mechanisms that facilitate glioblastoma multiforme cell survival and growth within the tumor microenvironment are largely unknown. We applied digital karyotyping and single nucleotide polymorphism arrays to screen for copy-number changes in glioblastoma multiforme samples and found that the most frequently amplified region is at chromosome 7p11.2. The high resolution of digital karyotyping and single nucleotide polymorphism arrays permits the precise delineation of amplicon boundaries and has enabled identification of the minimal region of amplification at chromosome 7p11.2, which contains two genes, EGFR and SEC61γ. SEC61γ encodes a subunit of a heterotrimeric protein channel located in the endoplasmic reticulum (ER). In addition to its high frequency of gene amplification in glioblastoma multiforme, SEC61γ is also remarkably overexpressed in 77% of glioblastoma multiforme but not in lower-grade gliomas. The small interfering RNA-mediated knockdown of SEC61γ expression in tumor cells led to growth suppression and apoptosis. Furthermore, we showed that pharmacologic ER stress agents induce SEC61γ expression in glioblastoma multiforme cells. Together, these results indicate that aberrant expression of SEC61γ serves significant roles in glioblastoma multiforme cell survival likely via a mechanism that is involved in the cytoprotective ER stress-adaptive response to the tumor microenvironment. [Cancer Res 2009;69(23):9105-11]

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Section: Discussionmentioning

confidence: 99%

Glioblastoma Proto-oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress

Zhou

Killela

et al. 2009

Cancer Research

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“…The DDX1 gene has been mapped to chromosome 2p24, ϳ400 kb telomeric to the proto-oncogene MYCN (Amler et al, 1996;Kuroda et al, 1996;Noguchi et al, 1996;Pandita et al, 1997). MYCN, a member of the myc family of transcription factors, is amplified and overexpressed in approximately one-third of all neuroblastoma (NB) tumors as well as in Ͻ10% of RB tumors (Brodeur et al, 1984;Seeger et al, 1985;Sakai et al, 1988;Doz et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…HnRNP U or scaffold attachment factor A, a protein located in the nuclear matrix, has recently been shown to function as a repressor of RNA polymerase II elongation by inhibiting transcription factor TFIIH-mediated carboxyl-terminal domain phosphorylation (Kim and Nikodem, 1999). Interestingly, the domain common to both hnRNP U and DDX1 was found to mediate binding of TFIIH to the RNA polymerase II holoenzyme.The DDX1 gene has been mapped to chromosome 2p24, ϳ400 kb telomeric to the proto-oncogene MYCN (Amler et al, 1996;Kuroda et al, 1996;Noguchi et al, 1996;Pandita et al, 1997). MYCN, a member of the myc family of transcription factors, is amplified and overexpressed in approximately one-third of all neuroblastoma (NB) tumors as well as in Ͻ10% of RB tumors (Brodeur et al, 1984;Seeger et al, 1985;Sakai et al, 1988;Doz et al, 1996).…”

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confidence: 99%

Association of Human DEAD Box Protein DDX1 with a Cleavage Stimulation Factor Involved in 3′-End Processing of Pre-mRNA

Bléoo

Sun

Hendzel

et al. 2001

MBoC

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DEAD box proteins are putative RNA helicases that function in all aspects of RNA metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing. Because many processes involving RNA metabolism are spatially organized within the cell, we examined the subcellular distribution of a human DEAD box protein, DDX1, to identify possible biological functions. Immunofluorescence labeling of DDX1 demonstrated that in addition to widespread punctate nucleoplasmic labeling, DDX1 is found in discrete nuclear foci ϳ0.5 m in diameter. Costaining with anti-Sm and anti-promyelocytic leukemia (PML) antibodies indicates that DDX1 foci are frequently located next to Cajal (coiled) bodies and less frequently, to PML bodies. Most importantly, costaining with anti-CstF-64 antibody indicates that DDX1 foci colocalize with cleavage bodies. By microscopic fluorescence resonance energy transfer, we show that labeled DDX1 resides within a Fö rster distance of 10 nm of labeled CstF-64 protein in both the nucleoplasm and within cleavage bodies. Coimmunoprecipitation analysis indicates that a proportion of CstF-64 protein resides in the same complex as DDX1. These studies are the first to identify a DEAD box protein associating with factors involved in 3Ј-end cleavage and polyadenylation of pre-mRNAs. INTRODUCTIONDEAD box proteins are a family of putative RNA helicases found in all cellular organisms and in some viruses. They are characterized by eight conserved amino acid motifs, including the core DEAD (Asp-Glu-Ala-Asp) motif involved in ATP hydrolysis and coupling of ATPase and RNA helicase activity (Pause and Sonenberg, 1992). At least 14 human DEAD box proteins have been identified to date, summarized in the DExH/D protein family database (Jankowsky and Jankowsky, 2000). DEAD box proteins are thought to modulate RNA secondary structure in all cellular processes involving RNA, including transcription, pre-mRNA processing, ribosome biogenesis, RNA export, translation initiation, and RNA degradation (Schmid and Linder, 1992;de la Cruz et al., 1999). Although many of the biological functions of the prokaryotic and lower eukaryotic DEAD box proteins have been identified, DEAD box proteins in higher eukaryotes remain largely uncharacterized.DDX1 is a human DEAD box protein that was identified by differential screening of a cDNA library enriched in transcripts present in two retinoblastoma (RB) cell lines: Y79 and RB522A (Godbout and Squire, 1993). The 2.7-kb DDX1 transcript encodes a protein with a predicted molecular mass of 82.4 kDa (Godbout et al., 1998). In addition to the eight conserved DEAD box family motifs, DDX1 also contains a region with homology to heterogeneous nuclear ribonucleoprotein U (hnRNP U) (Godbout et al., 1994). HnRNP U or scaffold attachment factor A, a protein located in the nuclear matrix, has recently been shown to function as a repressor of RNA polymerase II elongation by inhibiting transcription factor TFIIH-mediated carboxyl-terminal domain phosphorylation (Kim and Nikodem, 1999). Interestingly, the ...

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“…Previous reports have found elevated levels of DEAD‐box proteins in many tumors including breast cancer, testicular carcinoma, and neuroblastoma 8. In neuroblastoma, DDX1 is often, but not always, coamplified with the MYCN oncogene, due to close physical proximity to the MYCN oncogene 22, 23. MYCN amplification in neuroblastoma is strongly associated with poor disease prognosis.…”

Section: Discussionmentioning

confidence: 98%

“…8 In neuroblastoma, DDX1 is often, but not always, coamplified with the MYCN oncogene, due to close physical proximity to the MYCN oncogene. 22,23 MYCN amplification in neuroblastoma is strongly associated with poor disease prognosis. However, large series have shown that DDX1 coamplification with MYCN can actually result in improved clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node‐negative breast cancer

Taunk¹,

Goyal

Wu³

et al. 2011

Cancer

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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 ¼ .01). DDX1 positivity was found to be associated with improved local relapse-free survival (96% vs 85%, P ¼ .0233), distant metastaticfree survival (95% vs 85%, P ¼ .0320), and overall survival (92% vs 84%, P ¼ .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. Cancer 2012;118:888-

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The DDX1 gene maps within 400 kbp 5′ to MYCN and is frequently coamplified in human neuroblastoma

Cited by 10 publications

References 0 publications

Glioblastoma Proto-oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress

Glioblastoma Proto-oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress

Association of Human DEAD Box Protein DDX1 with a Cleavage Stimulation Factor Involved in 3′-End Processing of Pre-mRNA

DEAD box 1 (DDX1) expression predicts for local control and overall survival in early stage, node‐negative breast cancer

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