Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer

@article{Ju2014OriginsAF,
  title={Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer},
  author={Y. S. Ju and L. Alexandrov and M. Gerstung and I. Martincorena and S. Nik-Zainal and Manasa Ramakrishna and H. Davies and E. Papaemmanuil and A. Shlien and N. Bolli and S. Behjati and P. Tarpey and J. Nangalia and C. Massie and A. Butler and J. Teague and G. Vassiliou and M. Du and Ashwin Unnikrishnan and J. Pimanda and B. Teh and N. Munshi and M. Greaves and A. El‐Naggar and T. Santarius and V. P. Collins and R. Grundy and J. Taylor and D. Hayes and D. Malkin and C. Foster and H. Whitaker and T. Visakorpi and W. Isaacs and G. Bova and A. Flanagan and P. Futreal and A. Lynch and P. Chinnery and M. Stratton and P. Campbell and E. Provenzano and M. J. van de Vijver and A. Richardson and C. Purdie and S. Pinder and G. MacGrogan and A. Vincent-Salomon and D. Larsimont and D. Grabau and T. Sauer and {\O}. Garred and A. Ehinger and G. G. Van den Eynden and C. V. van Deurzen and R. Salgado and J. Brock and S. Lakhani and D. Giri and L. Arnould and J. Jacquemier and I. Treilleux and C. Caldas and S. Chin and Aquila Fatima and A. Thompson and A. Stenhouse and J. Foekens and J. Martens and A. Sieuwerts and Arjen Brinkman and H. Stunnenberg and P. Span and F. Sweep and C. Desmedt and C. Sotiriou and G. Thomas and A. Broeks and A. Langer{\o}d and S. Aparicio and P. Simpson and L. V. Veer and J. Eyfj{\"o}rd and H. Hilmarsd{\'o}ttir and J. J{\'o}nasson and A. B{\o}rresen-Dale and Ming Ta Michael Lee and B. Wong and B. K. Tee Tan and G. Hooijer and L. Malcovati and S. Tauro and J. Boultwood and A. Pellagatti and M. Groves and A. Sternberg and C. Gambacorti-Passerini and P. Vyas and E. Hellstr{\^o}m-Lindberg and D. Bowen and N. Cross and A. Green and M. Cazzola and C. Cooper and R. Eeles and D. Wedge and P. Van Loo and G. Gundem and B. Kremeyer and S. Edwards and N. Camacho and Z. Kote-Jarai and N. Dennis and S. Merson and Jorge Zamora and J. Kay and C. Corbishley and Sarah Thomas and Serena Nik-Zainai and S. O'meara and L. Matthews and Jeremy Clark and R. Hurst and R. Mithen and S. Cooke and K. Raine and David Jones and A. Menzies and L. Stebbings and Jonathan Hinton and S. McLaren and L. Mudie and C. Hardy and Elizabeth Anderson and O. Joseph and V. Goody and B. Robinson and M. Maddison and Stephen J. Gamble and C. Greenman and D. Berney and S. Hazell and N. Livni and C. Fisher and C. Ogden and Pardeep Kumar and C. Woodhouse and D. Nicol and E. Mayer and T. Dudderidge and N. Shah and V. Gnanapragasam and A. Futreal and D. Easton and A. Warren and U. McDermott and D. Brewer and D. Neal},
  journal={eLife},
  year={2014},
  volume={3}
}
Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This… Expand
Simultaneous DNA and RNA Mapping of Somatic Mitochondrial Mutations across Diverse Human Cancers
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The distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing provides clues to the mechanism by which de novo mutations arise as well as how the genome is replicated and argues against alternative replication models. Expand
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Dramatic tumor- and tissue-specific variations in selective pressures suggest that cancer cells with advantageous levels of damaged mitochondrial genomes will selectively proliferate to facilitate the tumorigenic process. Expand
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The described properties of mtDNA mutational spectrum shed light on mtDNA replication, mtDNA evolution of mammals and can be used as a marker of cell longevity in single-cell analyses of heterogeneous samples. Expand
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Ex vivo replication-associated events underlie mtDNA mutagenesis in DLBCL and preferentially generate functionally consequential mutations, yet mtDNA somatic mutations remain selectively neutral, suggesting that mtDNA-encoded mitochondrial functions may not play an important role inDLBCL. Expand
Mitochondrial mutational spectrum in mammals is sensitive to cellular and organismal longevity by means of A>G transitions
​150 max: Mutational spectrum of the mitochondrial genome (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra betweenExpand
Landscape of Germline and Somatic Mitochondrial DNA Mutations in Pediatric Malignancies.
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This pan-cancer mtDNA study establishes the landscape of germline and tumor mt DNA mutations and identifies hotspots of tumor mtDNA mutations to pinpoint key mitochondrial functions in pediatric malignancies and suggests that deleterious mtDNA mutated play a role in the development and progression of pediatric cancers. Expand
Mitochondrial mutations in human cancer: Curation of translation
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The cancer-derived mutations occurring in the DNA of the mitochondrion are analyzed and the need to universally regard the important differences between the standard and mitochondrial genetic code in life science research is highlighted. Expand
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