Targeted resequencing of the microRNAome and 3′UTRome reveals functional germline DNA variants with altered prevalence in epithelial ovarian cancer

被引：21

作者：

Chen, X. ^{[1
,2
]}

Paranjape, T. ^{[3
]}

Stahlhut, C. ^{[1
]}

McVeigh, T. ^{[4
,5
]}

Keane, F. ^{[6
]}

Nallur, S. ^{[3
]}

Miller, N. ^{[4
,5
]}

Kerin, M. ^{[4
,5
]}

Deng, Y. ^{[7
]}

Yao, X. ^{[7
]}

Zhao, H. ^{[2
,8
,9
]}

Weidhaas, J. B. ^{[3
]}

Slack, F. J. ^{[1
]}

机构：

[1] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA

[3] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA

[4] Natl Univ Ireland Galway, Discipline Surg, Galway, Ireland

[5] Galway Univ, Hosp, Galway, Ireland

[6] Yale Univ, Sch Med, New Haven, CT 06520 USA

[7] Yale Univ, Sch Med, Yale Ctr Analyt Sci, New Haven, CT 06520 USA

[8] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA

[9] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA

来源：

ONCOGENE | 2015年 / 34卷 / 16期

关键词：

SINGLE NUCLEOTIDE POLYMORPHISMS; ACUTE MYELOID-LEUKEMIA; LARGE GENE LISTS; SOMATIC MUTATIONS; PCM1-JAK2; FUSION; BINDING-SITES; BREAST-CANCER; KRAS-VARIANT; RISK; GENOME;

D O I：

10.1038/onc.2014.117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ovarian cancer is a major cause of cancer deaths, yet there have been few known genetic risk factors identified, the best known of which are disruptions in protein coding sequences (BRCA1 and 2). Recent findings indicate that there are powerful genetic markers of cancer risk outside of these regions, in the noncoding mRNA control regions. To identify additional cancer-associated, functional non-protein-coding sequence germline variants associated with ovarian cancer risk, we captured DNA regions corresponding to all validated human microRNAs and the 3' untranslated regions (UTRs) of similar to 6000 cancer-associated genes from 31 ovarian cancer patients. Multiple single-nucleotide polymorphisms in the 3'UTR of the vascular endothelial growth factor receptor/FLT1, E2F2 and PCM1 oncogenes were highly enriched in ovarian cancer patients compared with the 1000 Genome Project. Sequenom validation in a case-control study (267 cases and 89 controls) confirmed a novel variant in the PCM1 3'UTR is significantly associated with ovarian cancer (P = 0.0086). This work identifies a potential new ovarian cancer locus and further confirms that cancer resequencing efforts should not ignore the study of noncoding regions of cancer patients.

引用

页码：2125 / 2137

页数：13

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