Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer

Kimberly A. Zuhlke, Anna M. Johnson, Scott A. Tomlins, Nallasivam Palanisamy, John D. Carpten, Ethan M. Lange, William B. Isaacs, Kathleen A. Cooney

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)983-990
Number of pages8
Issue number9
StatePublished - Jun 2014


  • candidate linkage region
  • familial
  • gene

ASJC Scopus subject areas

  • Oncology
  • Urology


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