Abstract 1642: Rare missense variants in MAP3K14 and ARHGAP27 in men with hereditary prostate cancer

Background: Linkage studies have consistently identified the 17q21-22 chromosomal region to be important in hereditary prostate cancer, although no known causal variant has yet been identified. Three genes in this region are potential candidates based on known function as well as location in our region of interest. Mitogen-activated protein kinase kinase kinase 14 (MAP3k14) encodes a serine-threonine protein kinase that stimulates NF-κβ activity. The ARHGAP27 gene codes for a Rho-like small GTPase-activating protein and RND2 is part of the Rho GTPase family implicated in endosomal trafficking. Methods: All exons within the 17q21-22 chromosomal region were interrogated in 94 probands from hereditary prostate cancer families and linkage to the 17q21-22 region. Participants were from the University of Michigan Prostate Cancer Genetics Project and Johns Hopkins University. Enrichment was performed using the RainDance Technology following an emulsion PCR protocol. Sequencing was performed on the ABI SOLiD platform. Confirmation of mutation status among family members (both affected and unaffected) was performed using Sanger sequencing. Results: No deleterious truncating mutations were detected in the three candidate genes. Although missense variants were not observed in RND2, five missense variants were identified in the MAP3k14 and ARHGAP27 genes. Four of the five variants are novel (not described in dbSNP) and four out of the five variants are predicted to be damaging on protein function by SIFT and/or PolyPhen. Several of these variants demonstrated evidence of cosegregation within families based on sequencing of family members. Conclusions: We have identified five missense variants in MAP3k14 and ARHGAP27 in men with hereditary prostate cancer. Further research is ongoing in the laboratory to determine the frequency of these variants in a large prostate cancer case-control study.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1642. doi:1538-7445.AM2012-1642

Duke Scholars

Author Kathleen Ann Cooney Medicine, Medical Oncology