The awakening of an advanced malignant cancer: An insult to the mitochondrial genome

• Published in: Biochimica et biophysica acta Vol. 1820; no. 5; pp. 652 - 662
• Main Authors: Cook, Cody C., Higuchi, Masahiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2012
• Subjects: Cancer; Depletion; Disease Progression; DNA, Mitochondrial - genetics; early development; fermentation; Genome, Mitochondrial; Humans; metastasis; Mitochondria; Mitochondrial DNA; mitochondrial genome; Mutation; Mutation - genetics; Neoplasms - etiology; Neoplasms - pathology; phenotype; phenotypes; Mitochondria; Mitochondrial DNA; Depletion; Mutation; Cancer
• ISSN: 0304-4165; 0006-3002; 1872-8006; 0006-3002
• DOI: 10.1016/j.bbagen.2011.08.017

In only months-to-years a primary cancer can progress to an advanced phenotype that is metastatic and resistant to clinical treatments. As early as the 1900s, it was discovered that the progression of a cancer to the advanced phenotype is often associated with a shift in the metabolic profile of the disease from a state of respiration to anaerobic fermentation — a phenomenon denoted as the Warburg Effect. Reports in the literature strongly suggest that the Warburg Effect is generated as a response to a loss in the integrity of the sequence and/or copy number of the mitochondrial genome content within a cancer. Multiple studies regarding the progression of cancer indicate that mutation, and/or, a flux in the copy number, of the mitochondrial genome content can support the early development of a cancer, until; the mutational load and/or the reduction-to-depletion of the copy number of the mitochondrial genome content induces the progression of the disease to an advanced phenotype. Collectively, evidence has revealed that the human cell has incorporated the mitochondrial genome content into a cellular mechanism that, when pathologically actuated, can de(un)differentiate a cancer from the parental tissue of origin into an autonomous disease that disrupts the hierarchical structure-and-function of the human body. This article is part of a Special Issue entitled: Biochemistry of Mitochondria. ►This review describes change in mitochondrial genome in cancer. ►Evidence shows that mitochondrial genome is predisposed to mutation in carcinogenesis. ►Then a burst of mutations occurred associated with advanced malignant phenotype.