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


Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.

DOI: 10.1101/gr.190470.115

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@article{Ju2015FrequentST, title={Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.}, author={Young Seok Ju and Jose M. C. Tubio and William Mifsud and Beiyuan Fu and H. Davies and Manasa Ramakrishna and Yilong Li and Lucy R. Yates and Gunes Gundem and P. Tarpey and Sam Behjati and Elli Papaemmanuil and Sancha Martin and Anthony Fullam and Moritz Gerstung and Jyoti Nangalia and Anthony R Green and Carlos Caldas and {\AA}ke Borg and Andrew N Tutt and Ming Ta Michael Lee and Laura J. van't Veer and Benita Kiat Tee Tan and Samuel Aparicio and Paul N Span and John W M Martens and Stian Knappskog and Anne Vincent-Salomon and Anne-Lise B\orresen-Dale and J{\'o}runn Erla Eyfj{\"{o}rd and Ola Myklebost and Adrienne Margaret Flanagan and Christopher S Foster and David E. Neal and Colin S Cooper and Rosalind A Eeles and Steven Bova and Sunil R Lakhani and Christine Desmedt and Gilles D. Thomas and Andrea L. Richardson and Colin A. Purdie and Alastair M. Thompson and Ultan McDermott and Fengtang Yang and Serena Nik-Zainal and Peter J. Campbell and Michael R. Stratton}, journal={Genome research}, year={2015}, volume={26 5}, pages={717.2} }