Mutational landscape of candidate genes in familial prostate cancer. Issue 14 (11th August 2014)

• Record Type: Journal Article
• Authors: Johnson, Anna M.; Zuhlke, Kimberly A.; Plotts, Chris; McDonnell, Shannon K.; Middha, Sumit; Riska, Shaun M.; Schaid, Daniel J.; Thibodeau, Stephen N.; Douglas, Julie A.; Cooney, Kathleen A.
• Is Part Of: Prostate. Volume 74:Issue 14(2014)
• Page Start: 1371
• Page End: 1378
• Publication Date: 2014-08-11
• Subjects: Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22849
• Languages: English
• ISSNs: 0270-4137

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pros22849-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>Family history is a major risk factor for prostate cancer (PCa), suggesting a genetic component to the disease. However, traditional linkage and association studies have failed to fully elucidate the underlying genetic basis of familial PCa.</p> </sec> <sec id="pros22849-sec-0002" sec-type="section"> <title>METHODS</title> <p>Here, we use a candidate gene approach to identify potential PCa susceptibility variants in whole exome sequencing data from familial PCa cases. Six hundred ninety‐seven candidate genes were identified based on function, location near a known chromosome 17 linkage signal, and/or previous association with prostate or other cancers. Single nucleotide variants (SNVs) in these candidate genes were identified in whole exome sequence data from 33 PCa cases from 11 multiplex PCa families (3 cases/family).</p> </sec> <sec id="pros22849-sec-0003" sec-type="section"> <title>RESULTS</title> <p>Overall, 4, 856 candidate gene SNVs were identified, including 1, 052 missense and 10 nonsense variants. Twenty missense variants were shared by all three family members in each family in which they were observed. Additionally, 15 missense variants were shared by two of three family members and predicted to be deleterious by five different algorithms. Four missense variants, <italic>BLM</italic> Gln123Arg, <italic>PARP2</italic> Arg283Gln, <italic>LRCC46</italic> Ala295Thr and <italic>KIF2B</italic> Pro91Leu, and one nonsense variant, <italic>CYP3A43</italic> Arg441Ter, showed complete co‐segregation with PCa status. Twelve additional variants displayed partial co‐segregation with PCa.</p> </sec> <sec id="pros22849-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>Forty‐three nonsense and shared, missense variants were identified in our candidate genes. Further research is needed to determine the contribution of these variants to PCa susceptibility. <italic>Prostate 74:1371–1378, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>