Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

http://genome.cshlp.org/content/early/2015/05/11/gr.190470.115.long

Young Seok Ju, Jose M.C. Tubio, Peter J. Campbell, Michael R. Stratton et al.

Mitochondrial DNA (mtDNA) is physically separated from nuclear DNA, with each being contained within separate double membranes. However, in this study, the authors show that mitochondrial-nuclear genome fusion events occur in cancer cells at a rate similar to nuclear interchromosomal rearrangements.

Across the samples investigated, the authors found 10 primary cancers (1.8%, 10/559) and 2 cancer cell lines (7.1%, 2/28) with somatic mtDNA integrations into their nuclear genomes. Of the 12 cancers, 2 had more than one mitochondrial-nuclear DNA translocation event (aside: suggesting that this is not a phenomenon one must worry about if trying to count mtDNA copy number in cancer, with techniques such as qPCR? But interesting nonetheless!). By counting the total amount of mtDNA in a cancer cell, the authors calculate that the average frequency of mitochondrial-nuclear DNA fusion is ~5.1e-3 junctions per million base pairs of mtDNA, which is about half the intranuclear interchromosomal translocation rate (1.2e-2 junctions per million bp of nDNA).

Further studies are required to determine the mechanism by which mtDNA and nDNA can overcome the physical barriers separating them. However, the authors note that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved, suggesting that these fusion events coincide with nuclear genomic rearrangements.