Analysis of microsatellite instability, TGF-beta type II receptor gene mutations and hMSH2 and hMLH1 allele losses in pancreaticobiliary maljunction-associated biliary tract tumors

While pancreaticobiliary maljunctions (PBM) are clearly associated with bil iary tract tumor development, little is known about their molecular mechani sms. This study was conducted to assess the contributions of microsatellite instability (MSI) mutations of transforming growth factor type II receptor (TGF-beta RII) and insulin-like growth factor type II receptor (IGF RII) g enes and loss of heterozygosity (LOH) of hMSH2 and hMLH1 in 23 biliary trac t tumors using PCR methods. MSI was detected by 13 markers in 16/23 samples (69.6%). TGF-beta RII mutations were detected in eight of these (50%), and of the IGF IIR gene in two (12.5%). LOH was detected in 4/16 (25%) at the hMSH2 locus, and 2/16 (12.5%) at the hMLH1 locus No TGF-beta RII mutations or LOH of hMSH2 and hMLH1 were detected in MSI-negative samples. These find ings suggest that MSI plays an important role in carcinogenesis of the bili ary tract epithelium with PBM cases.