Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma

Background & Aims: Microsatellite instability (MSI) in mitochondrial DNA (m tDNA) is observed in some colorectal carcinomas. We attempted to determine if mitochondrial MSI (mtMSI) and mutations occur in gastric carcinomas and if the mtMSI phenotype underlies specific clinicopathologic profiles, Metho ds: Sixty-two gastric carcinomas (34 intestinal and 28 diffuse types) were investigated. Coding mutations in 8 different mitochondrial genes, mtMSI in a noncoding (C)n tract, and p53 gene mutations were examined by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis . MSI in nuclear DNA (nMSI) and loss of the p53 gene were examined using mi crosatellite markers. Results: Ten of 62 (16%) carcinomas showed the mtMSI phenotype. Mitochondrial gene mutation was detected in 5 carcinomas, 4 of w hich also showed the mtMSI phenotype. There was a positive correlation betw een mtMSI and nMSI status. In intestinal carcinomas, mtMSI, nMSI, and p53 g ene alterations were frequently detected from early to advanced stages. In diffuse carcinomas, both hinds of MSI were found in only advanced (subseros al or serosal invasion) carcinomas. Six of 7 carcinomas with the nMSI pheno type and all 5 carcinomas with mitochondrial coding mutations had a conside rable intestinal-type tumor cell component. Conclusions: Mitochondrial gene mutations, which are associated with the mtMSI phenotype, may play a speci fic role in the tumorigenesis of intestinal-type gastric carcinomas.