Mitochondrial DNA Copy Number Alterations in Human Cancers

Abstract

Mitochondria are cytoplasmic organelles that participate in adenosine triphosphate (ATP) production through respiration and oxidative phosphorylation (OXPHOS), free radical formation and execution of apoptosis. Perturbation of mitochondrial function has been proposed as one vital hallmark of cancer cells. Besides plenty of germline and polymorphic sequence variations accumulated in both coding and noncoding regions of the mitochondrial genome ( mitochondrial deoxyribonucleic acid (DNA); mtDNA), increased or reduced mtDNA copy number has also been increasingly described in a plethora of primary human malignancies. Altered mtDNA quantity may act as an important player in the multistep carcinogenesis of at least some types of human cancer by fuelling tumour initiation and/or advancement. In addition, mtDNA content turnover in bodily liquids from cancer patients could be exploited as a novel molecular tool for early cancer screening and diagnosis. Key Concepts: Disruption of mitochondrial function and the oxidative phosphorylation system may lead to cancer occurrence and development. MtDNA copy number changes have been frequently observed in a wide range of human malignancies. Aberrant mtDNA quantity is correlated with many key clinicopathological features of cancer patients. Alterations in mtDNA copy number have potential to affect cancer cell behaviours in vitro and in vivo . mtDNA content alterations could be considered as a novel biomarker for early cancer detection and diagnosis.

Circulating Mitochondrial DNA Level, a Noninvasive Biomarker for the Early Detection of Gastric Cancer

“…Despite all recent developments in molecular diagnostics (16), identification of biomarkers with reliable predictive value is still unavailable. Peripheral blood mtDNA copy number has recently emerged as a potential preventive/diagnosis biomarker associated with the risk of various cancers (18,19). Levels of circulating mtDNA were found significantly higher in patients with various type of tumors (29)(30)(31)(32)44).…”

“…Mitochondrial DNA (mtDNA) is a circular molecule present at 2 to 10 copies per organelle (17). Both mutations and alterations of mtDNA content have been described in many different cancer types (18)(19)(20). mtDNA mutations have been detected at early stages of gastric carcinogenesis (21,22).…”