Point mutations of the c-Ki-ras gene in carcinoma and atypical epithelium associated with congenital biliary dilation.

ABSTRACT

OBJECTIVES: Congenital biliary dilation (CBD) may be accompanied later by gallbladder carcinoma or bile duct carcinoma. These cancerous lesions are frequently associated with atypical epithelium that was suspected of being precancerous. To determine whether atypical epithelium may be precancerous, we examined the DNA sequence of the c-Ki-ras gene at codon 12 in nine cases of CBD concurrent with seven gallbladder carcinomas, one bile duct carcinoma, and one bile duct atypical epithelium. METHODS: Tumor specimens were surgically removed from nine patients with CBD at Nagoya University Hospital between 1979 and 1988. Tumor was isolated by microdissection, and DNA was amplified by a two-step polymerase chain reaction which then was directly sequenced. RESULTS: Four of seven gallbladder carcinomas and one bile duct carcinoma contained the c-Ki-ras point mutation at codon 12, and atypical epithelium associated with these carcinomas had the same mutation. One case of atypical bile duct epithelium also contained the mutation. CONCLUSIONS: These results indicate that the c-Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical epithelia associated with CBD.