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

Ju, Young Seok, Tubio, Jose M. C., Mifsud, William, Fu, Beiyuan, Davies, Helen R., Ramakrishna, Manasa, Li, Yilong, Yates, Lucy, Gundem, Gunes, Tarpey, Patrick S., Behjati, Sam, Papaemmanuil, Elli, Martin, Sancha, Fullam, Anthony, Gerstung, Moritz, Nangalia, Jyoti, Green, Anthony R., Caldas, Carlos, Borg, Åke, Tutt, Andrew, Lee, Ming Ta Michael, van'T Veer, Laura J., Tan, Benita K. T., Aparicio, Samuel, Span, Paul N., Martens, John W. M., Knappskog, Stian, Vincent-Salomon, Anne, Børresen-Dale, Anne-Lise, Eyfjörd, Jórunn Erla, Myklebost, Ola, Flanagan, Adrienne M., Foster, Christopher, Neal, David E., Cooper, Colin ORCID: https://orcid.org/0000-0003-2013-8042, Eeles, Rosalind, Bova, G. Steven, Lakhani, Sunil R., Desmedt, Christine, Thomas, Gilles, Richardson, Andrea L., Purdie, Colin A., Thompson, Alastair M., McDermott, Ultan, Yang, Fengtang, Nik-Zainal, Serena, Campbell, Peter J. and Stratton, Michael R. and ICGC Prostate Cancer Working Group, ICGC Bone Cancer Working Group, ICGC Breast Cancer Working Group (2015) Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells. Genome Research, 25 (6). pp. 814-824. ISSN 1088-9051

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	genetics,genetics(clinical),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1311
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Pure Connector
Date Deposited:	24 Jul 2015 22:50
Last Modified:	03 Nov 2022 15:38
URI:	https://ueaeprints.uea.ac.uk/id/eprint/53727
DOI:	10.1101/gr.190470.115

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