| Literature DB >> 28436987 |
Yi Kan Wang1, Ali Bashashati1, Michael S Anglesio2,3, Dawn R Cochrane1, Diljot S Grewal1,2, Gavin Ha1, Andrew McPherson1,2, Hugo M Horlings1, Janine Senz1, Leah M Prentice1, Anthony N Karnezis2, Daniel Lai1, Mohamed R Aniba1, Allen W Zhang1,4,5, Karey Shumansky1, Celia Siu1, Adrian Wan1, Melissa K McConechy2, Hector Li-Chang2, Alicia Tone2, Diane Provencher6,7,8, Manon de Ladurantaye6,7, Hubert Fleury6,7, Aikou Okamoto9, Satoshi Yanagida9, Nozomu Yanaihara9, Misato Saito9, Andrew J Mungall10, Richard Moore10, Marco A Marra10,11, C Blake Gilks2,12, Anne-Marie Mes-Masson6,7,13, Jessica N McAlpine3, Samuel Aparicio1,2, David G Huntsman1,2,3, Sohrab P Shah1,2,10.
Abstract
We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival. This finding was recapitulated in two independent cohorts (n = 576 cases), transcending BRCA1 and BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped according to APOBEC deamination (26%) and age-related mutational signatures (40%). ENOCs were divided by cases with microsatellite instability (28%), with a distinct mismatch-repair mutation signature. Taken together, our work establishes the potency of the somatic genome, reflective of diverse DNA repair deficiencies, to stratify ovarian cancers into distinct biological strata within the major histotypes.Entities:
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Year: 2017 PMID： 28436987 DOI： 10.1038/ng.3849
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330