Alterations in mtDNA: a qualitative and quantitative study associated with cervical cancer development.

OBJECTIVE

High-risk human papillomaviruses are the causative agent of cervical carcinogenesis. Additionally, a number of other unknown factors are also instrumental in the development of cancer. The aim of this present study was the analysis of the mutations in the D-loop region of mitochondrial DNA, and 4.997 bp deletion during cervical cancer development. Our research also extended to the relationship between mtDNA copy number, ROS (reactive oxygen species) production and the MnSOD (manganese superoxide dismutase) expression level.

METHODS

The study group consisted of postoperative tissues from patients diagnosed with L-SIL, H-SIL and squamous cell cervical carcinomas. A quantitative real-time polymerase chain reaction was used to determine the copy number of the mitochondrial DNA, and MnSOD mRNA expression levels. A PCR amplification and a sequencing of DNA were used for the identification of HPV DNA and mtDNA mutations.

RESULTS

A total of 62 point mutations in the D-loop region of mtDNA were found in study patients. The mitochondrial DNA copy number increased during cervical cancer development when compared to the corresponding tissues in the control samples. About 70% of the mtDNA copy number have a 4.997 bp deletion in L-SIL. We also observed an increase in ROS generation during cervical cancer development.

CONCLUSION

Alterations in mtDNA both qualitatively (by mutations) and quantitatively (by mtDNA copy number) are associated with cervical cancer developments. High levels of mtDNA copy with a 4.997 bp deletion in L-SIL cells can be associated with the susceptibility of cells to HPV persistent infection and cervical cancer development.