| Literature DB >> 27182968 |
Andrew McPherson1,2,3,4, Andrew Roth1,3, Emma Laks1, Tehmina Masud1,4, Ali Bashashati1, Allen W Zhang1,3,5, Gavin Ha1,3,6,7, Justina Biele1, Damian Yap1, Adrian Wan1, Leah M Prentice8, Jaswinder Khattra1, Maia A Smith1,3, Cydney B Nielsen4, Sarah C Mullaly1, Steve Kalloger1, Anthony Karnezis8, Karey Shumansky1, Celia Siu1, Jamie Rosner1, Hector Li Chan8, Julie Ho8, Nataliya Melnyk8, Janine Senz8, Winnie Yang8, Richard Moore9, Andrew J Mungall9, Marco A Marra9, Alexandre Bouchard-Côté10, C Blake Gilks11, David G Huntsman1,4,8, Jessica N McAlpine12, Samuel Aparicio1,4, Sohrab P Shah1,4,9.
Abstract
We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers.Entities:
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Year: 2016 PMID： 27182968 DOI： 10.1038/ng.3573
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330