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 biliary tract tumor development, little is known about their molecular mechanisms. 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) genes and loss of heterozygosity (LOH) of hMSH2 and hMLH1 in 23 biliary tract 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 findings suggest that MSI plays an important role in carcinogenesis of the biliary tract epithelium with PBM cases.
Nagai
M
M
First Department of Surgery, Mie University School of Medicine, Japan.
Kawarada
Y
Y
Watanabe
M
M
Iwase
T
T
Muneyuki
T
T
Yamao
K
K
Fukutome
K
K
Yatani
R
R
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000483:Alleles; D014670:Ampulla of Vater / Q000002:abnormalities*; D001652:Bile Ducts / Q000002:abnormalities*; D001661:Biliary Tract Neoplasms / Q000235:genetics*; D002352:Carrier Proteins; D000013:Congenital Abnormalities / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein