Genomic Evolution of Breast Cancer Metastasis and Relapse

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2017 Aug 16

PMID 28810143

Citations 356

Authors

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 Sawyer

Christine Desmedt

Christos Sotiriou

Michael R Stratton

Anieta M Sieuwerts

Andy G Lynch

John W Martens

Andrea L Richardson

Andrew Tutt

Per Eystein Lonning

Peter J Campbell

Affiliations

Soon will be listed here.

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.

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