title: Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer.
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.
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|School of Computing Science, Simon Fraser University, Burnaby, British Columbia, Canada.|Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Andrew
authors.identifier: 0000-0002-5654-5101
authors.initials: A
authors.lastname: McPherson
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Roth
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: Laks
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tehmina
authors.initials: T
authors.lastname: Masud
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Bashashati
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.|Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, British Columbia, Canada.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.|Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Ha
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Justina
authors.initials: J
authors.lastname: Biele
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Damian
authors.identifier: 0000-0002-5370-4592
authors.initials: D
authors.lastname: Yap
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Wan
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Prentice
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Jaswinder
authors.initials: J
authors.lastname: Khattra
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Maia A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cydney B
authors.initials: CB
authors.lastname: Nielsen
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Mullaly
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Kalloger
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Karnezis
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Karey
authors.initials: K
authors.lastname: Shumansky
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Celia
authors.initials: C
authors.lastname: Siu
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rosner
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Hector Li
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Ho
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Melnyk
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Janine
authors.initials: J
authors.lastname: Senz
authors.affiliation: Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Winnie
authors.initials: W
authors.lastname: Yang
authors.affiliation: Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.affiliation: Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Andrew J
authors.identifier: 0000-0002-0905-2742
authors.initials: AJ
authors.lastname: Mungall
authors.affiliation: Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
authors.affiliation: Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bouchard-Côté
authors.affiliation: Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|Centre for Translational and Applied Genomics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.affiliation: Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Sohrab P
authors.identifier: 0000-0001-6402-523X
authors.initials: SP
authors.lastname: Shah
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D005185:Fallopian Tube Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology*; D010802:Phylogeny; D059010:Single-Cell Analysis / Q000379:methods; D015996:Survival Rate; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor