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

Nat Genet
Authors
Keywords
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.

Year of Publication
2012
Journal
Nat Genet
Volume
44
Issue
6
Pages
685-9
Date Published
2012 May 20
ISSN
1546-1718
URL
DOI
10.1038/ng.2279
PubMed ID
22610119
PubMed Central ID
PMC3673022
Links
Grant list
P50 CA090381 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
P50 CA097186 / CA / NCI NIH HHS / United States
P50CA097186 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 CA125612 / CA / NCI NIH HHS / United States
DP2OD002750 / OD / NIH HHS / United States
DP2 OD002750 / OD / NIH HHS / United States
Howard Hughes Medical Institute / United States
U01CA111275 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States
T32 CA080416 / CA / NCI NIH HHS / United States