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

Christopher E. Barbieri, Sylvan C. Baca, Michael S. Lawrence, Francesca Demichelis, Mirjam Blattner, Jean Philippe Theurillat, Thomas A. White, Petar Stojanov, Eliezer Van Allen, Nicolas Stransky, Elizabeth Nickerson, Sung Suk Chae, Gunther Boysen, Daniel Auclair, Robert C. Onofrio, Kyung Park, Naoki Kitabayashi, Theresa Y. MacDonald, Karen Sheikh, Terry VuongCandace Guiducci, Kristian Cibulskis, Andrey Sivachenko, Scott L. Carter, Gordon Saksena, Douglas Voet, Wasay M. Hussain, Alex H. Ramos, Wendy Winckler, Michelle C. Redman, Kristin Ardlie, Ashutosh K. Tewari, Juan Miguel Mosquera, Niels Rupp, Peter J. Wild, Holger Moch, Colm Morrissey, Peter S. Nelson, Philip W. Kantoff, Stacey B. Gabriel, Todd R. Golub, Matthew Meyerson, Eric S. Lander, Gad Getz, Mark A. Rubin, Levi A. Garraway

Research output: Contribution to journalArticlepeer-review

1201 Scopus citations


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.

Original languageEnglish
Pages (from-to)685-689
Number of pages5
JournalNature Genetics
Issue number6
StatePublished - Jun 2012
Externally publishedYes


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