The evolutionary history of 2,658 cancers
(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.
(Less)
- author
- contributor
- Borg, Åke
LU
; Ringnér, Markus
LU
and Staaf, Johan
LU
- author collaboration
- organization
- publishing date
- 2020-02
- 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
-
- scopus:85079055162
- pmid:32025013
- 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
- 2024-06-29 04:47:25
@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}},
}