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Chen, X; Paranjape, T; Stahlhut, C; McVeigh, T; Keane, F; Nallur, S; Miller, N; Kerin, M; Deng, Y; Yao, X; Zhao, H; Weidhaas, J B; Slack, F J
Oncogene, 04/2015, Letnik: 34, Številka: 16Journal Article
Ovarian cancer is a major cause of cancer deaths, yet there have been few known genetic risk factors identied, the best known of which are disruptions in protein coding sequences (BRCA1 and 2). Recent ndings 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 ~ 6000 cancer-associated genes from 31 ovarian cancer patients. Multiple single-nucleotide polymorphisms in the 3UTR 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 casecontrol study (267 cases and 89 controls) conrmed a novel variant in the PCM1 3UTR 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.
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