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Updated: Aug 13, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Microsatellite instability, mitochondrial DNA large deletions, and mitochondrial DNA mutations in gastric carcinoma
1Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Dr. Roberto Frias s/n, 4200 Porto, Portugal. vmaximo@ipatimup.pt
Abstract:
Mitochondrial DNA (mtDNA) large deletions and mtDNA mutations have been demonstrated in various types of human cancer. The relationship between the occurrence of such alterations and the nuclear microsatellite instability (MSI) status of the neoplastic cells remains controversial. In an attempt to clarify the situation in gastric carcinoma, we studied, by PCR/SSCP and sequencing, five mitochondrial genes and two D-loop regions in 32 gastric carcinomas that had been previously screened for MSI and mitochondrial common deletion. MtDNA alterations were detected in 26 carcinomas (81%). All the mtDNA mutations, which occurred mainly in the D-loop and ND1 and ND5 genes, were transitions. D-loop alterations (insertions and/or deletions) were not significantly associated with mutations in the coding regions. There was a trend towards an inverse relationship between the occurrence of mitochondrial common deletion and mtDNA mutations. No significant relationship was observed between MSI status and mtDNA mutations, whereas the mitochondrial common deletion appeared to be almost exclusively restricted to MSI-negative tumors. The latter finding--almost no gastric carcinoma with MSI-positive phenotype has large deletions of mtDNA--needs to be confirmed in a larger series and in tumors from other organs.
Insights
Mitochondrial DNA (mtDNA) mutations are common in gastric cancer but not linked to microsatellite instability (MSI). However, large mtDNA deletions are predominantly found in MSI-negative tumors, suggesting a potential link.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Mitochondrial DNA (mtDNA) alterations, including large deletions and mutations, are observed in various human cancers.
- The association between these mtDNA changes and nuclear microsatellite instability (MSI) status in cancer cells is not well-established.
Purpose of the Study:
- To investigate the relationship between mtDNA alterations (mutations and common deletions) and MSI status in gastric carcinoma.
- To characterize the types and locations of mtDNA mutations in gastric cancer.
Main Methods:
- Analysis of five mitochondrial genes and two D-loop regions using PCR/SSCP and sequencing in 32 gastric carcinoma samples.
- Samples were pre-screened for MSI and mitochondrial common deletion.
- Characterization of mtDNA mutations, including transitions, insertions, and deletions.
Main Results:
- Mitochondrial DNA alterations were detected in 81% of gastric carcinomas.
- Mutations primarily occurred in the D-loop, ND1, and ND5 genes, predominantly as transitions.
- Mitochondrial common deletion showed a trend towards an inverse relationship with mtDNA mutations and was significantly associated with MSI-negative tumors.
Conclusions:
- Mitochondrial DNA mutations in gastric cancer are not significantly related to MSI status.
- Mitochondrial common deletions are largely restricted to MSI-negative gastric carcinomas, a finding that warrants further investigation in larger cohorts and other cancer types.
