The prognostic effects of somatic mutations in ER-positive breast cancer.
Date
2018-09-04ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Breast Neoplasms
MAP Kinase Kinase Kinase 1
Neurofibromin 1
Receptors, Estrogen
Prognosis
Survival Analysis
Case-Control Studies
Cohort Studies
Postmenopause
Mutation
Adult
Middle Aged
Female
Phosphatidylinositol 3-Kinases
Class I Phosphatidylinositol 3-Kinases
Discoidin Domain Receptor 1
Research team
Endocrinology
Language
eng
Date accepted
2018-07-05
License start date
2018-09-04
Citation
Nature communications, 2018, 9 (1), pp. 3476 - ?
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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