| Literature DB >> 30181556 |
Obi L Griffith1,2,3,4, Nicholas C Spies1, Meenakshi Anurag5,6, Malachi Griffith1,2,3,4, Jingqin Luo3,7, Dongsheng Tu8, Belinda Yeo9, Jason Kunisaki1, Christopher A Miller1,2, Kilannin Krysiak1,2, Jasreet Hundal1, Benjamin J Ainscough1, Zachary L Skidmore1, Katie Campbell1, Runjun Kumar2, Catrina Fronick1, Lisa Cook1, Jacqueline E Snider2, Sherri Davies2, Shyam M Kavuri5,6, Eric C Chang5,6, Vincent Magrini1,4,10, David E Larson1, Robert S Fulton1,4, Shuzhen Liu8, Samuel Leung8, David Voduc8, Ron Bose2, Mitch Dowsett9, Richard K Wilson1,3,4, Torsten O Nielsen8, Elaine R Mardis11,12,13,14, Matthew J Ellis15,16.
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.Entities:
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Year: 2018 PMID： 30181556 PMCID： PMC6123466 DOI： 10.1038/s41467-018-05914-x
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919