Mitochondrial DNA mutations in light-associated skin tumors

Mutations of mitochondrial DNA (mtDNA) have been proposed to be involved in carcinogenesis. In this study, we applied the polymerase chain reaction techniques to investigate the frequency of occurrence and proportion of mtDNA with length mutations (deletions and tandem duplications) in light-associated skin tumors (actinic keratosis, AK; basal cell carcinoma, BCC; and squamous cell carcinoma, SCC) in aged individuals. We demonstrated the existence of multiple mtDNA deletions and tandem duplications in tissues of AK, BCC, SCC and normal skin. We showed that the frequencies of occurrence of the 4,977 bp and 7,436 bp deletions and tandem duplications (200 bp and 260 bp) of mtDNA in light-associated skin tumors were not significantly different from those of sun-exposed normal skin (p>0.05), but higher than those of non-exposed normal skin (p<0.05). In addition, we found that the proportion of the 4,977 bp-deleted mtDNA in the skin of the same individual was also affected by skin pathologies. The proportion of 4,977 bp-deleted mtDNA in relatively rapid growing tumor cells in SCC was lower than that of normal skin cells. We suggest that the existence of these length mutations of mtDNA in normal, precancerous or cancerous human skin may be attributed to the stochastic effect of photo-damage. However, it is unclear whether the mutations of mtDNA have a direct bearing on carcinogenesis in skin. Future investigation is warranted to elucidate the causal relationship between mtDNA mutations and skin cancers and to address the pathophysiological role of mtDNA mutations in skin cancer development.