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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 and Tarpey, Patrick S, et al. (2015) In Genome Research 25(6). p.814-824
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... (More)
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. (Less)
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Contribution to journal
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published
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Genome Research
volume
25
issue
6
pages
814 - 824
publisher
Cold Spring Harbor Laboratory Press
external identifiers
  • pmid:25963125
  • wos:000355565900004
  • scopus:84931830812
ISSN
1549-5469
DOI
10.1101/gr.190470.115
project
CREATE Health
language
English
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yes
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f9544e49-29e3-4fa9-b9cc-01d737f99863 (old id 5453392)
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http://www.ncbi.nlm.nih.gov/pubmed/25963125?dopt=Abstract
date added to LUP
2015-06-03 12:02:54
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2017-11-19 03:02:23
@article{f9544e49-29e3-4fa9-b9cc-01d737f99863,
  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.},
  author       = {Ju, Young Seok and Tubio, Jose M C and Mifsud, William and Fu, Beiyuan and Davies, Helen R and Ramakrishna, Manasa and Li, Yilong and Yates, Lucy and Gundem, Gunes and Tarpey, Patrick S and Behjati, Sam and Papaemmanuil, Elli and Martin, Sancha and Fullam, Anthony and Gerstung, Moritz and Nangalia, Jyoti and Green, Anthony R and Caldas, Carlos and Borg, Åke and Tutt, Andrew and Lee, Ming Ta Michael and Van't Veer, Laura J and Tan, Benita K T and Aparicio, Samuel and Span, Paul N and Martens, John W M and Knappskog, Stian and Vincent-Salomon, Anne and Børresen-Dale, Anne-Lise and Eyfjörd, Jórunn Erla and Flanagan, Adrienne M and Foster, Christopher and Neal, David E and Cooper, Colin and Eeles, Rosalind and Lakhani, Sunil R and Desmedt, Christine and Thomas, Gilles and Richardson, Andrea L and Purdie, Colin A and Thompson, Alastair M and McDermott, Ultan and Yang, Fengtang and Nik-Zainal, Serena and Campbell, Peter J and Stratton, Michael R},
  issn         = {1549-5469},
  language     = {eng},
  number       = {6},
  pages        = {814--824},
  publisher    = {Cold Spring Harbor Laboratory Press},
  series       = {Genome Research},
  title        = {Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.},
  url          = {http://dx.doi.org/10.1101/gr.190470.115},
  volume       = {25},
  year         = {2015},
}