Accession Number:

ADA413554

Title:

CHK2, A Candidate Prostate Cancer Susceptibility Gene

Descriptive Note:

Annual rept. 1 Jan-31 Dec 2002

Corporate Author:

MAYO CLINIC ROCHESTER MN

Personal Author(s):

Report Date:

2003-01-01

Pagination or Media Count:

20.0

Abstract:

To identify prostate cancer susceptibility genes, we applied a mutation screening of candidate gene approach. We screened for mutations in CHEK2, the upstream regulator of p53 in the DNA-damage-signaling pathway, in DNA samples isolated from 178 clinic tumors, 149 familial prostate cancer HPC families, 400 sporadic cases, and 423 unaffected men as control. A total of 28 4.8 germline CHEK2 mutations were found among 578 patients and additional 11 in 9 families. Sixteen of 18 unique CHEK2 mutations identified in this study were not detected among 423 unaffected men, suggesting a pathological effect of CHEK2 mutations in prostate cancer development. Analyses of the two frameshift mutations in Epstein Barr virus-transformed cell lines using RT-PCR and Western blot analysis, revealed abnormal splicing of one mutation and dramatic reduction of CHEK protein levels in both cases. Overall. Our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development prostate cancer.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE