Mitochondrial Genome Microsatellite Instability and Copy Number Alteration in Lung Carcinomas

Objective: Mitochondrial DNA (mtDNA) is considered a hotspot of mutations in various tumors. However, therelationship between microsatellite instability (MSI) and mtDNA copy number alterations in lung cancer has yetto be fully clarifieds. In the current study, we investigated the copy number and MSI of mitochondrial genomein lung carcinomas, as well as their significance for cancer development.
Methods: The copy number and MSIof mtDNA in 37 matched lung carcinoma/adjacent histological normal lung tissue samples were examined bypolymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assays for sequence variation,followed by sequence analysis and fluorogenic 5’-nuclease real-time PCR. Student’s t test and linear regressionanalyses were employed to analyze the association between mtDNA copy number alterations and mitochondrialMSI (mtMSI).
Results: The mean copy number of mtDNA in lung carcinoma tissue samples was significantlylower than that of the adjacent histologically normal lung tissue samples (p < 0.001). mtMSI was detected in 32.4%(12/37) of lung carcinoma samples. The average copy number of mtDNA in lung carcinoma samples containingmtMSI was significantly lower than that in the other lung carcinoma samples (P < 0.05).
Conclusions: Resultssuggest that mtMSI may be an early and important event in the progression of lung carcinogenesis, particularlyin association with variation in mtDNA copy number.