Title | Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat J-P, White TA, Stojanov P, Van Allen E, Stransky N, Nickerson E, Chae S-S, Boysen G, Auclair D, Onofrio RC, Park K, Kitabayashi N, MacDonald TY, Sheikh K, Vuong T, Guiducci C, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Hussain WM, Ramos AH, Winckler W, Redman MC, Ardlie K, Tewari AK, Mosquera JMiguel, Rupp N, Wild PJ, Moch H, Morrissey C, Nelson PS, Kantoff PW, Gabriel SB, Golub TR, Meyerson M, Lander ES, Getz G, Rubin MA, Garraway LA |
Journal | Nat Genet |
Volume | 44 |
Issue | 6 |
Pagination | 685-9 |
Date Published | 2012 Jun |
ISSN | 1546-1718 |
Keywords | Exome, Hepatocyte Nuclear Factor 3-alpha, Humans, Male, Mediator Complex, Microtubule-Associated Proteins, Mutation, Prostatic Neoplasms, Sequence Analysis, DNA |
Abstract | Prostate cancer is the second most common cancer in men worldwide and causes over 250,000 deaths each year. Overtreatment of indolent disease also results in significant morbidity. Common genetic alterations in prostate cancer include losses of NKX3.1 (8p21) and PTEN (10q23), gains of AR (the androgen receptor gene) and fusion of ETS family transcription factor genes with androgen-responsive promoters. Recurrent somatic base-pair substitutions are believed to be less contributory in prostate tumorigenesis but have not been systematically analyzed in large cohorts. Here, we sequenced the exomes of 112 prostate tumor and normal tissue pairs. New recurrent mutations were identified in multiple genes, including MED12 and FOXA1. SPOP was the most frequently mutated gene, with mutations involving the SPOP substrate-binding cleft in 6-15% of tumors across multiple independent cohorts. Prostate cancers with mutant SPOP lacked ETS family gene rearrangements and showed a distinct pattern of genomic alterations. Thus, SPOP mutations may define a new molecular subtype of prostate cancer. |
DOI | 10.1038/ng.2279 |
Alternate Journal | Nat. Genet. |
PubMed ID | 22610119 |
PubMed Central ID | PMC3673022 |
Grant List | DP2 OD002750 / OD / NIH HHS / United States DP2OD002750 / OD / NIH HHS / United States P50 CA090381 / CA / NCI NIH HHS / United States P50CA097186 / CA / NCI NIH HHS / United States R01 CA125612 / CA / NCI NIH HHS / United States R01 CA125612 / CA / NCI NIH HHS / United States T32 CA080416 / CA / NCI NIH HHS / United States T32 GM007753 / GM / NIGMS NIH HHS / United States U01 CA111275 / CA / NCI NIH HHS / United States U01CA111275 / CA / NCI NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States U54 HG003067 / HG / NHGRI NIH HHS / United States / / Howard Hughes Medical Institute / United States |