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

• Main Authors: Barbieri, Christopher E. (Author), Baca, Sylvan C. (Author), Lawrence, Michael S. (Author), Demichelis, Francesca (Author), Blattner, Mirjam (Author), Theurillat, Jean-Philippe (Author), White, Thomas A. (Author), Stojanov, Petar (Author), Van Allen, Eliezer (Author), Stransky, Nicolas (Author), Nickerson, Elizabeth (Author), Chae, Sung-Suk (Author), Boysen, Gunther (Author), Auclair, Daniel (Author), Onofrio, Robert (Author), Park, Kyung (Author), Kitabayashi, Naoki (Author), MacDonald, Theresa Y. (Author), Sheikh, Karen (Author), Lander, Eric Steven (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Lander, Eric S. (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2014-02-03T20:16:49Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Human Genome Research Institute (U.S.) (Large Scale Sequencing Program Grant U54 HG003067)