Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-07

AUTHORS

Andrew McPherson, Andrew Roth, Emma Laks, Tehmina Masud, Ali Bashashati, Allen W Zhang, Gavin Ha, Justina Biele, Damian Yap, Adrian Wan, Leah M Prentice, Jaswinder Khattra, Maia A Smith, Cydney B Nielsen, Sarah C Mullaly, Steve Kalloger, Anthony Karnezis, Karey Shumansky, Celia Siu, Jamie Rosner, Hector Li Chan, Julie Ho, Nataliya Melnyk, Janine Senz, Winnie Yang, Richard Moore, Andrew J Mungall, Marco A Marra, Alexandre Bouchard-Côté, C Blake Gilks, David G Huntsman, Jessica N McAlpine, Samuel Aparicio, Sohrab P Shah

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. More... »

PAGES

758-767

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3573

DOI

http://dx.doi.org/10.1038/ng.3573

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046917301

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27182968


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484 rdf:type schema:Organization
485 https://www.grid.ac/institutes/grid.248762.d schema:alternateName BC Cancer Agency
486 schema:name Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
487 Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
488 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
489 Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
490 rdf:type schema:Organization
491 https://www.grid.ac/institutes/grid.412541.7 schema:alternateName Vancouver General Hospital
492 schema:name Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
493 rdf:type schema:Organization
494 https://www.grid.ac/institutes/grid.66859.34 schema:alternateName Broad Institute
495 schema:name Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
496 Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
497 Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
498 Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
499 rdf:type schema:Organization
 




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