Mitochondrial DNA as a Cancer Biomarker
Circulating cell-free (ccf) mtDNA in blood is a non-invasive diagnostic and prognostic biomarker for many forms of solid tumors. Plasma or serum ccf mtDNA levels are significantly different between cancer patients and healthy individuals (Yu 2012). Leukocyte mtDNA content is an independent prognostic biomarker complementing TNM (tumor-nodes-metastasis) stage and associated with immunosuppression in CRC patients (Qu et al. 2015). Circulating levels of mtDNA and IL8, as measured by quatitative real-time PCR, constitute a potential biomarker for the early detection of gastric cancer (Fernandes et al. 2014). Additionally, leukocyte mtDNA content might serve as a potential biomarker to select CRC patients who will benefit from adjuvant chemotherapy. Heteroplasmic and homoplasmic sequence variants occur in the mitochondrial genome in tumors of patients. These changes can be identified by sequencing mitochondrial DNA (mtDNA) obtained from tumors and blood from the same individual. Rapid and high-throughput sequencing has been used for the detection of sequence variants in mtDNA. Relatively simple diagnostic tests for detecting mtDNA mutations, involving mitochondrial microarrays and real-time PCR, have predictive potential for cancer detection and prognosis. mtDNA DNA alterations (mutations, deletions and instability) are emerging as biomarkers for detecting a variety of cancers in tissue samples and biofluids which can be included in population screening studies. Using a oligonucleotide microarray (MitoChip) for rapid sequencing of the entire mitochondrial genome, somatic mtDNA alterations were observed in preneoplastic lesions even in the absence of histopathologic evidence of dysplasia. A 3.4-kb mitochondrial genome deletion (3.4 mtdelta) was reported to be useful for molecular definition of benign, malignant, and proximal to malignant prostate needle biopsy specimens (Maki et al. 2008). These findings support the rationale for exploring the mitochondrial genome as a biomarker for the early diagnosis of cancer.