The prognostic effects of somatic mutations in ER-positive breast cancer
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 04, 2018
- Source ID
- 10.1038/s41467-018-05914-x
Entities
People
- Belinda Yeo
- Benjamin J Ainscough
- Catrina Fronick
- Christopher A. Miller
- David E Larson
- David Voduc
- Dongsheng Tu
- Elaine R. Mardis
- Eric C. Chang
- Jacqueline E. Snider
- Jason Kunisaki
- Jasreet Hundal
- Jingqin Luo
- Katie Campbell
- Kilannin Krysiak
- Lisa Cook
- Malachi Griffith
- Matthew J Ellis
- Meenakshi Anurag
- Mitch Dowsett
- Nicholas C. Spies
- Obi Griffith
- Richard K. Wilson
- Robert S. Fulton
- Ron Bose
- Runjun Kumar
- Samuel Leung
- Sherri R Davies
- Shuzhen Liu
- Shyam M. Kavuri
- Torsten O. Nielsen
- Vincent Magrini
- Zachary L. Skidmore
Organizations
- Cancer Prevention and Research Institute of Texas
- Susan G. Komen for the Cure
- United States Department of Defense