Mitochondria are cellular organelles that play an essential role in eukaryotes, producing the energy needed for a cell to survive. Beyond the ~3.2 Gb of nuclear genomic DNA, each human cell has hundreds of mitochondria which carry one or a few copies of the 16.5 kb circular mitochondria DNA (mtDNA). Despite its small size, the circular genome encodes 37 genes, including 13 proteins that generate respiratory chain complexes together with other proteins of nuclear origin. Similar to nuclear genome, mtDNA in cancer cells frequently harbor somatically acquired alterations. Whole-genome or whole-exome sequencing of the tumor and its matched normal tissues (frequently blood or adjacent non-tumor tissues) enables sensitive and efficient detection of somatic mtDNA mutations. Because each cancer cell commonly carries hundreds to thousands of mtDNA copies, detection of mtDNA mutations is dependent on the heteroplasmic level of each mutation. Here, we describe strategies to accurately identify somatic mtDNA mutations in cancer genome studies.
Keywords: Bioinformatics; Genome sequencing; Genomics; Heteroplasmy; Mitochondria; Next-generation sequencing; Somatic mutations.
© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.