CHK2, A Candidate Prostate Cancer Susceptibility Gene
Abstract
To identify prostate cancer susceptibility genes, we applied a mutation screening of candidate gene approach. In our last year's reporter, we identified a total of 28 (4.8%) germline CHEK2 mutations in 178 clinic tumors, 149 familial prostate cancer (HPC) families, and 400 sporadic cases. Sixteen of the 18 unique CHK2 mutations identified in this study were not detected among 423 unaffected men, suggesting a pathological effect of CHK2 mutations in prostate cancer development. In this year's reporter, we identified two somatic CHK2 mutations in 84 clinic prostate tumor samples indicating that CHK2 mutation in prostate cancer could be both germline or somatic. To investigate the function of these mutations in prostate tumorigenesis, we generated stable cell lines and analyzed the CHK2 kinase activities in 9 of the mutants before and after irradiation. While most of the mutations have modest reduced CHK2 kinase activity in comparison with wild-type CHK2, one somatic mutation (Glu321Lys) totally abolishes kinase activity. Our data provide first evidence that the CHK2 mutations identified in prostate cancer, both germline and somatic, impair CHK2 kinase activity suggesting that mutations in CHK2 may contribute to the development of prostate cancer through altering CHK2 kinase activity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA423213
Entities
People
- Wanguo Liu
Organizations
- Mayo Clinic