TY - JOUR
T1 - The prognostic effects of somatic mutations in ER-positive breast cancer
AU - Griffith, Obi L.
AU - Spies, Nicholas C.
AU - Anurag, Meenakshi
AU - Griffith, Malachi
AU - Luo, Jingqin
AU - Tu, Dongsheng
AU - Yeo, Belinda
AU - Kunisaki, Jason
AU - Miller, Christopher A.
AU - Krysiak, Kilannin
AU - Hundal, Jasreet
AU - Ainscough, Benjamin J.
AU - Skidmore, Zachary L.
AU - Campbell, Katie
AU - Kumar, Runjun
AU - Fronick, Catrina
AU - Cook, Lisa
AU - Snider, Jacqueline E.
AU - Davies, Sherri
AU - Kavuri, Shyam M.
AU - Chang, Eric C.
AU - Magrini, Vincent
AU - Larson, David E.
AU - Fulton, Robert S.
AU - Liu, Shuzhen
AU - Leung, Samuel
AU - Voduc, David
AU - Bose, Ron
AU - Dowsett, Mitch
AU - Wilson, Richard K.
AU - Nielsen, Torsten O.
AU - Mardis, Elaine R.
AU - Ellis, Matthew J.
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85052751323&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05914-x
DO - 10.1038/s41467-018-05914-x
M3 - Article
C2 - 30181556
AN - SCOPUS:85052751323
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3476
ER -