Mitochondrial DNA Alterations in Cancer

Abstract

A number of studies have demonstrated the presence of mitochondrial DNA (mtDNA) mutations in cancer cells. In this article, we review mitochondrial genomic aberrations reported in solid tumors of the breast, colon, stomach, liver, kidney, bladder, head/neck, and lung. The tantalizing association of tumors with mtDNA mutations implicates these mutations in the process of carcinogenesis. Alterations in expression of mtDNA transcripts in a variety of cancer types are also reviewed. In solid tumors, elevated expression of mtDNA-genes coding for subunits of the mitochondrial electron respiratory chain may reflect mitochondrial adaptation to perturbations in cellular energy requirements. The role of mtDNA mutations and altered expression of mitochondrial genes in carcinogenesis is discussed. Mitochondrial DNA mutations can initiate a cascade of events leading to a continuous increase in the production of reactive oxygen species (persistent oxidative stress), a condition that probably favors tumor development.

Mitochondrial D-Loop Polymorphism and Microsatellite Instability in Prostate Cancer and Benign Hyperplasia Patients

“…Mutations in mtDNA can cause impairment of oxidative phosphorylation and increase ROS production which in turn accelerates the DNA mutation rate (Pang et al, 2008). It is reported that the mutation frequency in mtDNA is about 10-to 20-fold greater as compared to nuclear DNA (Copeland et al, 2002). Mitochondrial DNA mutations are present in both coding and non-coding regions and most of them appeared to be homoplasmic in nature (Chatterjee et al, 2006).…”

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

“…Qualitative aberrations of mtDNA, such as mutations, have been found in solid tumours, such as colon, stomach, liver, kidney, bladder, prostate, skin and lung cancer (Copeland et al 2002;Penta et al 2001), and in haematological malignancies, such as leukaemia and lymphoma (Fontenay et al 2006). Quantitative aberrations of mtDNA have been observed in various sample types from patients with cancers (Mambo et al 2005).…”

Glucose Metabolism in Breast Cancer and its Implication in Cancer Therapy

“…The role of mitochondria-derived ROS has also been implicated in a proposed vicious cycle linking mtDNA mutation in tumors. On the one hand, a burst of ROS production from mitochondria would favour oxidative dependent mitochondrial mutagenesis and hence promote tumorigenesis [37]; While on the other hand, mutation of mtDNA in the respiratory chain components could commence a cascade of events leading to an increase in electron leakage and ROS over-generation in the process of malignant transformation and tumor progression [38,39]. Several mtDNA mutations have been found in breast tumors [40], and the presence of mtDNA mutations in breast cancer cells is consistent with the intrinsic susceptibility of mtDNA to damage and persistent oxidative stress [41].…”