Barbieri CE, Baca SC, Lawrence MS, Demichelis F, Blattner M, Theurillat JP, White TA, Stojanov P, Van Allen E, Stransky N, et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet. 2012;44:685–9.
NOTES
Barbieri, Christopher EBaca, Sylvan CLawrence, Michael SDemichelis, FrancescaBlattner, MirjamTheurillat, Jean-PhilippeWhite, Thomas AStojanov, PetarVan Allen, EliezerStransky, NicolasNickerson, ElizabethChae, Sung-SukBoysen, GuntherAuclair, DanielOnofrio, Robert CPark, KyungKitabayashi, NaokiMacDonald, Theresa YSheikh, KarenVuong, TerryGuiducci, CandaceCibulskis, KristianSivachenko, AndreyCarter, Scott LSaksena, GordonVoet, DouglasHussain, Wasay MRamos, Alex HWinckler, WendyRedman, Michelle CArdlie, KristinTewari, Ashutosh KMosquera, Juan MiguelRupp, NielsWild, Peter JMoch, HolgerMorrissey, ColmNelson, Peter SKantoff, Philip WGabriel, Stacey BGolub, Todd RMeyerson, MatthewLander, Eric SGetz, GadRubin, Mark AGarraway, Levi AengP50 CA090381/CA/NCI NIH HHS/U54 HG003067/HG/NHGRI NIH HHS/P50 CA097186/CA/NCI NIH HHS/P50CA097186/CA/NCI NIH HHS/T32 GM007753/GM/NIGMS NIH HHS/R01 CA125612/CA/NCI NIH HHS/DP2OD002750/OD/NIH HHS/DP2 OD002750/OD/NIH HHS/Howard Hughes Medical Institute/U01CA111275/CA/NCI NIH HHS/U01 CA111275/CA/NCI NIH HHS/T32 CA080416/CA/NCI NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Nat Genet. 2012 May 20;44(6):685-9. doi: 10.1038/ng.2279.
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.
Last updated on 02/17/2021