Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression

Abstract

Energy metabolism reprogramming was recently identified as one of the cancer hallmarks. One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA (mtDNA). In the past decades, several types of somatic mtDNA alterations have been identified in gastric cancer. However, the role of these mtDNA alterations in gastric cancer progression remains unclear. In this review, we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer. The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed. We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers. The two primary mutation types (transition mutations and mononucleotide or dinucleotide repeat instability) imply potential causative factors. Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer. The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.

Keywords: Gastric cancer; Somatic mitochondrial DNA mutations; Mitochondrial dysfunction

Core tip: In this review, we summarize recent somatic mitochondrial DNA (mtDNA) alterations identified in gastric cancer, and the relationship between these alterations and the clinicopathological features of gastric cancer. We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that potentially result in mitochondrial dysfunction in gastric cancer. Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer. The search for strategies to prevent the mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.