Heteroplasmic mutation of mitochondrial DNA D-loop and 4977-bp deletion in human cancer cells during mitochondrial DNA depletion.
Somatic mutations in mitochondrial DNA (mtDNA) have been demonstrated in various human cancers. Many cancers have high frequently of mtDNA with homoplasmic point mutations, and carry less frequently of mtDNA with large-scale deletions as compared with corresponding non-cancerous tissue. Moreover, most cancers harbor a decreased copy number of mtDNA than their corresponding non-cancerous tissue. However, it is unclear whether the process of decreasing in mtDNA content would be involved in an increase in the heteroplasmic level of somatic mtDNA point mutation, and/or involved in a decrease in the proportion of mtDNA with large-scale deletion in cancer cells. In this study, we provided evidence that the heteroplasmic levels of variations in cytidine number in np 303-309 poly C tract of mtDNA in three colon cancer cells were not changed during an ethidium bromide-induced mtDNA depleting process. In the mtDNA depleting process, the proportions of mtDNA with 4977-bp deletion in cybrid cells were not significantly altered. These results suggest that the decreasing process of mtDNA copy number per se may neither contribute to the shift of homoplasmic/heteroplasmic state of point mutation in mtDNA nor to the decrease in proportion of mtDNA with large-scale deletions in cancer cells. Mitochondrial genome instability and reduced mtDNA copy number may independently occur in human cancer.
Lee
Hsin-Chen
HC
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112, Republic of China. hclee2@ym.edu.tw
Hsu
Li-Sung
LS
Yin
Pen-Hui
PH
Lee
Liang-Ming
LM
Chi
Chin-Wen
CW
D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004996:Ethidium / Q000494:pharmacology; D017353:Gene Deletion; D006801:Humans; D006822:Hybrid Cells; D009369:Neoplasms / Q000235:genetics*; D017354:Point Mutation
D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D004996:Ethidium