Point Mutations of K-ras Gene in Children With Congenital Biliary Dilatation

Abstract

Purpose : Congenital biliary dilatation (CBD) with a pancreaticobiliary maljunction was thought to be an important risk factor for biliary tract carcinoma in Japan. However, the mechanism of carcinogenesis is unknown. Forty-five cases of congenital biliary dilatation were analyzed for the presence of K-ras gene point mutations. Pancreaticobiliary maljunction was confirmed in 27 of these patients. Methods : K-ras mutations were examined using genomic DNA extracted from histologic specimens resected at the time of surgery. DNA was analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing. Results : 22 of the 45 cases (44%) showed point mutations of K-ras codons 12 and 13. A direct sequence analysis of the K-ras gene revealed that mutation of codon 12 substituted GGT (glycine) for GAT (aspartic acid) in 13 cases and mutation of codon 13 substituted GGC (glycine) for AGC (serine) in 9 cases. Conclusions : Mutation of the K-ras gene may represent an early event in the pathogenesis of biliary tract carcinoma.