Scientific Publications

Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer.

Publication TypeJournal Article
AuthorsBarbieri, CE, Baca SC, Lawrence MS, Demichelis F., Blattner M., Theurillat JP, White TA, Stojanov P., Van Allen E., Stransky N., Nickerson E., Chae SS, 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 JM, Rupp N., Wild PJ, Moch H., Morrissey C., Nelson PS, Kantoff PW, Gabriel SB, Golub T. R., Meyerson M., Lander E. S., Getz G., Rubin MA, and Garraway LA
AbstractProstate 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.
Year of Publication2012
JournalNature genetics
Date Published (YYYY/MM/DD)2012/05/20
ISSN Number1061-4036