Genomic Evolution of Breast Cancer Metastasis and Relapse.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2017-08-14
Date Accepted
2017-07-14
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.
Citation
Cancer cell, 2017, 32 (2), pp. 169 - 184.e7
Source Title
Publisher
CELL PRESS
ISSN
1535-6108
eISSN
1878-3686