Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor(TGFbetaRII) gene have been detected in several human cancer typesexhibiting microsatellite instability. Using intron primers previouslyreported for examination of the entire coding region of the TGFbetaRIIgene, 29 sporadic gastric cancers were screened with non-radioactive singlestrand conformation polymorphism and subsequent DNA sequencing analysis.Mutations of the TGFbetaRII gene were detected in three out of 29 tumors(10%). Two cases showed deletions in a polyadenine tract in both allelesand was positively associated with replication error. One case had aninsertion of GA dinucleotide sequence in one allele. Mutations of theTGFbetaRII gene were restricted to exon 3 and other coding regions were notaffected. Loss of heterozygosity was detected by analyzing a polymorphicsite in intron 2. Three out of nine (33%) informative cases, which were allof intestinal type and advanced cases, showed loss of heterozygosity butneither TGFbetaRII mutation nor replication error was found in these cases.Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a differentextent in the gastric cancer with genetically abnormal transforming growthfactor. Although the numbers studied are small, homozygous (A)10 deletionor loss of heterozygosity of TGFbetaRII is involved in tumorigenesis andprogression of at least some part of sporadic gastric cancer.