Detection of mutated c-Ki-ras in the bile of patients with pancreatic cancer.
BACKGROUND: Because treatment of advanced pancreatic cancer is often unsuccessful, early detection is important. Codon 12 c-Ki-ras mutations have been found in 80-90% of pancreatic cancer cases and are a potential early marker for pancreatic cancer, but obtaining tissue or fluid for analysis can be difficult. We therefore evaluated whether mutant c-Ki-ras could be detected in bile samples obtained from pancreatic cancer patients. METHODS: DNA was isolated from bile specimens obtained from 20 patients with pancreatic cancer. The mutant-enriched PCR technique (ME-PCR) was used to amplify and detect point mutations at codon 12 of the c-Ki-ras oncogene. RESULTS: In 17 cases sufficient DNA for amplification was obtained; 14 had mutant c-Ki-ras alleles. Cytological evaluation of the bile was performed in 11 of these cases, but was positive in only two cases; both were positive for codon 12 c-Ki-ras mutations. Of the 9 cytologically negative biliary specimens, ME-PCR was positive in six. CONCLUSIONS: Codon 12 c-Ki-ras mutations can be successfully identified in PCR-amplified DNA from bile samples obtained from patients with advanced pancreatic cancer. This technique may supplement cytologic techniques for diagnosing pancreatic cancer and may be capable of identifying individuals at risk for this disease.
Abbruzzese, JL; Evans, DB; Raijman, I; Larry, L; King, T; Leach, SD; Frazier, ML
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