The prognostic effects of somatic mutations in ER-positive breast cancer.

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ICR Authors

Dowsett, Mitch

Authors

Griffith, OL
Spies, NC
Anurag, M
Griffith, M
Luo, J
Tu, D
Yeo, B
Kunisaki, J
Miller, CA
Krysiak, K
Hundal, J
Ainscough, BJ
Skidmore, ZL
Campbell, K
Kumar, R
Fronick, C
Cook, L
Snider, JE
Davies, S
Kavuri, SM
Chang, EC
Magrini, V
Larson, DE
Fulton, RS
Liu, S
Leung, S
Voduc, D
Bose, R
Dowsett, M
Wilson, RK
Nielsen, TO
Mardis, ER
Ellis, MJ

Document Type

Journal Article

Date

2018-09-04

Date Accepted

2018-07-05

Abstract

Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.

Citation

Nature communications, 2018, 9 (1), pp. 3476 - ?

DOI

10.1038/s41467-018-05914-x

URI

https://repository.icr.ac.uk/handle/internal/3311

Rights

https://creativecommons.org/licenses/by/4.0

Source Title

Publisher

NATURE PUBLISHING GROUP

ISSN

2041-1723

eISSN

2041-1723

Collections

Breast Cancer Research
Cancer Biology

Research Team

Endocrinology

Notes