Mitochondria in tumour progression: a network of mtDNA variants in different types of cancer.

ABSTRACT

BACKGROUND: Mitochondrial participation in tumorigenesis and metastasis has been studied for many years, but several aspects of this mechanism remain unclear, such as the association of mitochondrial DNA (mtDNA) with different cancers. Here, based on two independent datasets, we modelled an mtDNA mutation-cancer network by systematic integrative analysis including 37 cancer types to identify the mitochondrial variants found in common among them. RESULTS: Our network showed mtDNA associations between gastric cancer and other cancer types, particularly kidney, liver, and prostate cancers, which is suggestive of a potential role of such variants in the metastatic processes among these cancer types. A graph-based interactive web tool was made available at www2.lghm.ufpa.br/mtdna. We also highlighted that most shared variants were in the MT-ND4, MT-ND5 and D-loop, and that some of these variants were nonsynonymous, indicating a special importance of these variants and regions regarding cancer progression, involving genomic and epigenomic alterations. CONCLUSIONS: This study reinforces the importance of studying mtDNA in cancer and offers new perspectives on the potential involvement of different mitochondrial variants in cancer development and metastasis.