Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer
Version of Record online: 6 MAY 2014
© 2014 Wiley Periodicals, Inc.
Volume 74, Issue 9, pages 983–990, June 2014
How to Cite
Zuhlke, K. A., Johnson, A. M., Tomlins, S. A., Palanisamy, N., Carpten, J. D., Lange, E. M., Isaacs, W. B. and Cooney, K. A. (2014), Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer. Prostate, 74: 983–990. doi: 10.1002/pros.22818
- Issue online: 18 MAY 2014
- Version of Record online: 6 MAY 2014
- Manuscript Accepted: 11 APR 2014
- Manuscript Received: 26 MAR 2014
- candidate linkage region
Family history of prostate cancer is a well-recognized risk factor. Previous linkage studies have reported a putative prostate cancer susceptibility locus at chromosome 17q21–22. SPOP (Speckle-type POZ protein) maps to the 17q21–22 candidate linkage region and is one of the most frequently mutated genes in sporadic prostate cancers.
We performed targeted next generation sequencing to analyze 2009 exons from 202 genes in a candidate linkage region on chromosome 17q21–22 using 94 unrelated familial prostate cancer cases from the University of Michigan Prostate Cancer Genetics Project (n = 54) and Johns Hopkins University (n = 40) including the exons and UTRs of SPOP.
We identified a novel SPOP missense mutation (N296I) in a man with prostate cancer diagnosed at age 43. This mutation completely segregates with prostate cancer affection status among the men in this family. The N296I mutation resides within the evolutionarily conserved Bric-a-brac, Tramtrack, Broad-complex (BTB) domain, involved in recruiting targets to Cul3 for degradation. Analysis of the prostate tumor from this individual verified the presence of heterozygous N296I as well as an ERG fusion.
We have discovered a novel mutation in SPOP that tracks with prostate cancer within a family and is predicted to be deleterious. Taken together, our results implicate SPOP as a candidate gene for hereditary prostate cancer. Prostate 74:983–990, 2014. © 2014 Wiley Periodicals, Inc.