Abstract
Changes in mitochondrial DNA (mtDNA) content in cancers have been reported with controversial results, probably due to small sample size and variable pathological conditions. In this study, mtDNA content in 302 breast tumor/surrounding normal tissue pairs were evaluated and correlated with the clinico-pathological characteristics of tumors. Overall, mtDNA content in tumor tissues is significantly lower than that in the surrounding normal tissues, P < 0.00001. MtDNA content in tumor tissues decreased with increasing tumor size. However, when the tumor is very large (>50 cm3), mtDNA content started to increase. Similarly, mtDNA content decreased from grades 0 and I to grade II tumors, but increased from grade II to grade III tumors. Tumors with somatic mtDNA alterations in coding region have significantly higher mtDNA content than tumors without somatic mtDNA alterations (P < 0.001). Tumors with somatic mtDNA alterations in the D-Loop region have significantly lower mtDNA content (P < 0.001). Patients with both low and high mtDNA content in tumor tissue have significantly higher hazard of death than patients with median levels of mtDNA content. mtDNA content in tumor tissues change with tumor size, grade, and ER/PR status; significant deviation from the median level of mtDNA content is associated with poor survival.
Highlights
Mitochondria are the small power houses of the human cells
Tumors with somatic mitochondrial DNA (mtDNA) alterations in the D-Loop region have significantly lower mtDNA content (P < 0.001). Patients with both low and high mtDNA content in tumor tissue have significantly higher hazard of death than patients with median levels of mtDNA content. mtDNA content in tumor tissues change with tumor size, grade, and ER/PR status; significant deviation from the median level of mtDNA content is associated with poor survival
About 65% (191/293) of tumor tissues have reduced mtDNA content when compared to their surrounding mtDNA content in tumor tissue
Summary
Mitochondria are the small power houses of the human cells. They consume oxygen to generate about 80%∼90% of the energy supply for the cell in the form of ATP and much of the endogenous reactive oxygen (ROS) via oxidative phosphorylation (OXPHOS). Mitochondria play an important role in programmed cell death through the release of cytochrome c from mitochondria to trigger a proteolytic cascade involving caspases. Depending on the cell type, each cell contains hundreds to thousands copies of mitochondrial DNA (mtDNA). Human mtDNA encodes 13 protein subunits of the respiratory chain as well as 2 rRNAs and a set of 22 tRNAs, essential for mitochondrial protein synthesis [1]
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