Skip to main content
Journal cover image

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

Publication ,  Journal Article
Zuhlke, KA; Johnson, AM; Tomlins, SA; Palanisamy, N; Carpten, JD; Lange, EM; Isaacs, WB; Cooney, KA
Published in: Prostate
June 2014

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.

Duke Scholars

Published In

Prostate

DOI

EISSN

1097-0045

Publication Date

June 2014

Volume

74

Issue

9

Start / End Page

983 / 990

Location

United States

Related Subject Headings

  • Repressor Proteins
  • Prostatic Neoplasms
  • Pedigree
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Mutation, Missense
  • Male
  • Immunohistochemistry
  • Humans
  • High-Throughput Nucleotide Sequencing
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zuhlke, K. A., Johnson, A. M., Tomlins, S. A., Palanisamy, N., Carpten, J. D., Lange, E. M., … Cooney, K. A. (2014). Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer. Prostate, 74(9), 983–990. https://doi.org/10.1002/pros.22818
Zuhlke, Kimberly A., Anna M. Johnson, Scott A. Tomlins, Nallasivam Palanisamy, John D. Carpten, Ethan M. Lange, William B. Isaacs, and Kathleen A. Cooney. “Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer.Prostate 74, no. 9 (June 2014): 983–90. https://doi.org/10.1002/pros.22818.
Zuhlke KA, Johnson AM, Tomlins SA, Palanisamy N, Carpten JD, Lange EM, et al. Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer. Prostate. 2014 Jun;74(9):983–90.
Zuhlke, Kimberly A., et al. “Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer.Prostate, vol. 74, no. 9, June 2014, pp. 983–90. Pubmed, doi:10.1002/pros.22818.
Zuhlke KA, Johnson AM, Tomlins SA, Palanisamy N, Carpten JD, Lange EM, Isaacs WB, Cooney KA. Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer. Prostate. 2014 Jun;74(9):983–990.
Journal cover image

Published In

Prostate

DOI

EISSN

1097-0045

Publication Date

June 2014

Volume

74

Issue

9

Start / End Page

983 / 990

Location

United States

Related Subject Headings

  • Repressor Proteins
  • Prostatic Neoplasms
  • Pedigree
  • Oncology & Carcinogenesis
  • Nuclear Proteins
  • Mutation, Missense
  • Male
  • Immunohistochemistry
  • Humans
  • High-Throughput Nucleotide Sequencing