Genomic Evolution of Breast Cancer Metastasis and Relapse.
View/ Open
Date
2017-08-14ICR Author
Author
Yates, LR
Knappskog, S
Wedge, D
Farmery, JHR
Gonzalez, S
Martincorena, I
Alexandrov, LB
Van Loo, P
Haugland, HK
Lilleng, PK
Gundem, G
Gerstung, M
Pappaemmanuil, E
Gazinska, P
Bhosle, SG
Jones, D
Raine, K
Mudie, L
Latimer, C
Sawyer, E
Desmedt, C
Sotiriou, C
Stratton, MR
Sieuwerts, AM
Lynch, AG
Martens, JW
Richardson, AL
Tutt, A
Lønning, PE
Campbell, PJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Breast Neoplasms
Neoplasm Metastasis
Neoplasm Recurrence, Local
Chromosomal Proteins, Non-Histone
Transcription Factors
Evolution, Molecular
Mutation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
STAT3 Transcription Factor
Janus Kinase 2
Biomarkers, Tumor
Language
eng
Date accepted
2017-07-14
License start date
2017-08
Citation
Cancer cell, 2017, 32 (2), pp. 169 - 184.e7
Publisher
CELL PRESS