Journal Article

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

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

2016

Overview

Sohrab Shah, Samuel Aparicio and colleagues analyze whole genomes and single cells from ovarian cancers in the peritoneal cavity to establish patterns of disease spread. They determine the clonal relationships between multiple tumor sites and characterize the migratory potential of genomically diverse clones. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 45/23 / 631/114/2785 / 692/699/67/1517/1709 / Aged / Agriculture / Animal Genetics and Genomics / Biomarkers, Tumor - genetics / Biomedicine / Breast cancer / Cancer Research / Clone Cells - metabolism / Clone Cells - pathology / Cloning / Cystadenocarcinoma, Serous - genetics / Cystadenocarcinoma, Serous - pathology / Data analysis / Deoxyribonucleic acid / Development and progression / Disease Progression / DNA / DNA repair / Evolution / Fallopian Tube Neoplasms - genetics / Fallopian Tube Neoplasms - pathology / Female / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Gene Function / Gene mutations / Genetic aspects / Genetic Variation - genetics / Genome, Human / Genomes / Health aspects / High-Throughput Nucleotide Sequencing - methods / Human Genetics / Humans / Identification and classification / Medical research / Middle Aged / Mutation / Mutation - genetics / Neoplasm Grading / Neoplasm Recurrence, Local - genetics / Neoplasm Recurrence, Local - pathology / Ovarian cancer / Ovarian Neoplasms - genetics / Ovarian Neoplasms - pathology / Patients / Peritoneal Neoplasms - genetics / Peritoneal Neoplasms - pathology / Phylogenetics / Phylogeny / Single-Cell Analysis - methods / Studies / Survival Rate / Trees / Tumor Microenvironment - genetics