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Nat Genet. 2016 Jul;48(7):758-67. doi: 10.1038/ng.3573. Epub 2016 May 16.

Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.

Author information

1
Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
2
School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada.
3
Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
4
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
5
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, British Columbia, Canada.
6
Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
7
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
8
Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
9
Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
10
Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
11
Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
12
Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada.

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.

PMID:
27182968
DOI:
10.1038/ng.3573
[Indexed for MEDLINE]

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