Genomic Evolution of Breast Cancer Metastasis and Relapse

Lucy R. Yates, Stian Knappskog, David Wedge, James H.R. Farmery, Santiago Gonzalez, Inigo Martincorena, Ludmil B. Alexandrov, Peter Van Loo, Hans Kristian Haugland, Peer Kaare Lilleng, Gunes Gundem, Moritz Gerstung, Elli Pappaemmanuil, Patrycja Gazinska, Shriram G. Bhosle, David Jones, Keiran Raine, Laura Mudie, Calli Latimer, Elinor SawyerChristine Desmedt, Christos Sotiriou, Michael R. Stratton, Anieta M. Sieuwerts, Andy G. Lynch, John W. Martens, Andrea L. Richardson, Andrew Tutt, Per Eystein Lønning, Peter J. Campbell

Research output: Contribution to journalArticlepeer-review

Abstract

Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.

Original languageEnglish (US)
Pages (from-to)169-184.e7
JournalCancer cell
Volume32
Issue number2
DOIs
StatePublished - Aug 14 2017
Externally publishedYes

Keywords

  • breast cancer
  • genomics
  • metastasis
  • relapse
  • somatic mutation

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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