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The evolutionary history of 2,658 cancers

Gerstung, Moritz ; Jolly, Clemency ; Leshchiner, Ignaty ; Dentro, Stefan C ; Gonzalez, Santiago ; Rosebrock, Daniel ; Mitchell, Thomas J ; Rubanova, Yulia ; Anur, Pavana and Yu, Kaixian , et al. (2020) In Nature 578(7793). p.122-128
Abstract

Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and... (More)

Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

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type
Contribution to journal
publication status
published
subject
keywords
DNA Repair/genetics, Evolution, Molecular, Gene Dosage, Genes, Tumor Suppressor, Genetic Variation, Genome, Human/genetics, Humans, Mutagenesis, Insertional/genetics, Neoplasms/genetics
in
Nature
volume
578
issue
7793
pages
122 - 128
publisher
Nature Publishing Group
external identifiers
  • pmid:32025013
  • scopus:85079055162
ISSN
0028-0836
DOI
10.1038/s41586-019-1907-7
language
English
LU publication?
yes
id
7f8ffa06-e8e9-402f-9107-0b4d690e5da6
date added to LUP
2023-03-29 17:11:59
date last changed
2024-06-15 03:34:51
@article{7f8ffa06-e8e9-402f-9107-0b4d690e5da6,
  abstract     = {{<p>Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.</p>}},
  author       = {{Gerstung, Moritz and Jolly, Clemency and Leshchiner, Ignaty and Dentro, Stefan C and Gonzalez, Santiago and Rosebrock, Daniel and Mitchell, Thomas J and Rubanova, Yulia and Anur, Pavana and Yu, Kaixian and Tarabichi, Maxime and Deshwar, Amit and Wintersinger, Jeff and Kleinheinz, Kortine and Vázquez-García, Ignacio and Haase, Kerstin and Jerman, Lara and Sengupta, Subhajit and Macintyre, Geoff and Malikic, Salem and Donmez, Nilgun and Livitz, Dimitri G and Cmero, Marek and Demeulemeester, Jonas and Schumacher, Steven and Fan, Yu and Yao, Xiaotong and Lee, Juhee and Schlesner, Matthias and Boutros, Paul C and Bowtell, David D and Zhu, Hongtu and Getz, Gad and Imielinski, Marcin and Beroukhim, Rameen and Sahinalp, S Cenk and Ji, Yuan and Peifer, Martin and Markowetz, Florian and Mustonen, Ville and Yuan, Ke and Wang, Wenyi and Morris, Quaid D and Spellman, Paul T and Wedge, David C and Van Loo, Peter}},
  issn         = {{0028-0836}},
  keywords     = {{DNA Repair/genetics; Evolution, Molecular; Gene Dosage; Genes, Tumor Suppressor; Genetic Variation; Genome, Human/genetics; Humans; Mutagenesis, Insertional/genetics; Neoplasms/genetics}},
  language     = {{eng}},
  number       = {{7793}},
  pages        = {{122--128}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature}},
  title        = {{The evolutionary history of 2,658 cancers}},
  url          = {{http://dx.doi.org/10.1038/s41586-019-1907-7}},
  doi          = {{10.1038/s41586-019-1907-7}},
  volume       = {{578}},
  year         = {{2020}},
}