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

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Abstract

Background and Aims: Microsatellite instability (MSI) in mitochondrial DNA (mtDNA) 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. Methods: 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 microsatellite markers. Results: Ten of 62 (16%) carcinomas showed the mtMSI phenotype. Mitochondrial gene mutation was detected in 5 carcinomas, 4 of which also showed the mtMSI phenotype. There was a positive correlation between mtMSI and nMSI status. In intestinal carcinomas, mtMSI, nMSI, and p53 gene alterations were frequently detected from early to advanced stages. In diffuse carcinomas, both kinds of MSI were found in only advanced (subserosal or serosal invasion) carcinomas. Six of 7 carcinomas with the nMSI phenotype and all 5 carcinomas with mitochondrial coding mutations had a considerable intestinal-type tumor cell component. Conclusions: Mitochondrial gene mutations, which are associated with the mtMSI phenotype, may play a specific role in the tumorigenesis of intestinal- type gastric carcinomas.

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Habano, W., Sugai, T., Nakamura, S. I., Uesugi, N., Yoshida, T., & Sasou, S. (2000). Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma. Gastroenterology, 118(5), 835–841. https://doi.org/10.1016/S0016-5085(00)70169-7

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