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 publication

DOI

10.1016/j.ccell.2017.07.005

Type

Journal article

Journal

Cancer cell

Publication Date

08/2017

Volume

32

Pages

169 - 184.e7

Addresses

Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK; Department of Clinical Oncology, Guys and St Thomas' NHS Trust, London SE1 9RT, UK.