The evolutionary history of 2,658 cancers

PCAWG Evolution & Heterogeneity Working Group; Moritz Gerstung; Clemency Jolly; Ignaty Leshchiner; Stefan C Dentro; Santiago Gonzalez; Daniel Rosebrock; Thomas J Mitchell; Yulia Rubanova; Pavana Anur; Kaixian Yu; Maxime Tarabichi; Amit Deshwar; Jeff Wintersinger; Kortine Kleinheinz; Ignacio Vázquez-García; Kerstin Haase; Lara Jerman; Subhajit Sengupta; Geoff Macintyre; Salem Malikic; Nilgun Donmez; Dimitri G Livitz; Marek Cmero; Jonas Demeulemeester; Steven Schumacher; Yu Fan; Xiaotong Yao; Juhee Lee; Matthias Schlesner; Paul C Boutros; David D Bowtell; Hongtu Zhu; Gad Getz; Marcin Imielinski; Rameen Beroukhim; S Cenk Sahinalp; Yuan Ji; Martin Peifer; Florian Markowetz; Ville Mustonen; Ke Yuan; Wenyi Wang; Quaid D Morris; Paul T Spellman; David C Wedge; Peter Van Loo; PCAWG Consortium

doi:10.1038/s41586-019-1907-7

The evolutionary history of 2,658 cancers

PCAWG Evolution & Heterogeneity Working Group, Moritz Gerstung, Clemency Jolly, Ignaty Leshchiner, Stefan C Dentro, Santiago Gonzalez, Daniel Rosebrock, Thomas J Mitchell, Yulia Rubanova, Pavana Anur, Kaixian Yu, Maxime Tarabichi, Amit Deshwar, Jeff Wintersinger, Kortine Kleinheinz, Ignacio Vázquez-García, Kerstin Haase, Lara Jerman, Subhajit Sengupta, Geoff MacintyreSalem Malikic, Nilgun Donmez, Dimitri G Livitz, Marek Cmero, Jonas Demeulemeester, Steven Schumacher, Yu Fan, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Paul C Boutros, David D Bowtell, Hongtu Zhu, Gad Getz, Marcin Imielinski, Rameen Beroukhim, S Cenk Sahinalp, Yuan Ji, Martin Peifer, Florian Markowetz, Ville Mustonen, Ke Yuan, Wenyi Wang, Quaid D Morris, Paul T Spellman, David C Wedge, Peter Van Loo, PCAWG Consortium

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English
Pages (from-to)	122-128
Number of pages	7
Journal	Nature
Volume	578
Issue number	7793
DOIs	https://doi.org/10.1038/s41586-019-1907-7
Publication status	Published - Feb 2020

Keywords

DNA Repair/genetics
Evolution, Molecular
Gene Dosage
Genes, Tumor Suppressor
Genetic Variation
Genome, Human/genetics
Humans
Mutagenesis, Insertional/genetics
Neoplasms/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41586-019-1907-7

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PCAWG Evolution & Heterogeneity Working Group, Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., Mitchell, T. J., Rubanova, Y., Anur, P., Yu, K., Tarabichi, M., Deshwar, A., Wintersinger, J., Kleinheinz, K., Vázquez-García, I., Haase, K., Jerman, L., Sengupta, S., ... PCAWG Consortium (2020). The evolutionary history of 2,658 cancers. Nature, 578(7793), 122-128. https://doi.org/10.1038/s41586-019-1907-7

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title = "The evolutionary history of 2,658 cancers",

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 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.",

keywords = "DNA Repair/genetics, Evolution, Molecular, Gene Dosage, Genes, Tumor Suppressor, Genetic Variation, Genome, Human/genetics, Humans, Mutagenesis, Insertional/genetics, Neoplasms/genetics",

author = "{PCAWG Evolution & Heterogeneity Working Group} and Moritz Gerstung and Clemency Jolly and Ignaty Leshchiner and Dentro, {Stefan C} and Santiago Gonzalez and Daniel Rosebrock and Mitchell, {Thomas J} and Yulia Rubanova and Pavana Anur and Kaixian Yu and Maxime Tarabichi and Amit Deshwar and Jeff Wintersinger and Kortine Kleinheinz and Ignacio V{\'a}zquez-Garc{\'i}a and Kerstin Haase and Lara Jerman and Subhajit Sengupta and Geoff Macintyre and Salem Malikic and Nilgun Donmez and Livitz, {Dimitri G} and Marek Cmero and Jonas Demeulemeester and Steven Schumacher and Yu Fan and Xiaotong Yao and Juhee Lee and Matthias Schlesner and Boutros, {Paul C} and Bowtell, {David D} and Hongtu Zhu and Gad Getz and Marcin Imielinski and Rameen Beroukhim and Sahinalp, {S Cenk} and Yuan Ji and Martin Peifer and Florian Markowetz and Ville Mustonen and Ke Yuan and Wenyi Wang and Morris, {Quaid D} and Spellman, {Paul T} and Wedge, {David C} and {Van Loo}, Peter and {PCAWG Consortium} and Andy Lynch",

year = "2020",

month = feb,

doi = "10.1038/s41586-019-1907-7",

language = "English",

volume = "578",

pages = "122--128",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature publishing group",

number = "7793",

}

PCAWG Evolution & Heterogeneity Working Group, Gerstung, M, Jolly, C, Leshchiner, I, Dentro, SC, Gonzalez, S, Rosebrock, D, Mitchell, TJ, Rubanova, Y, Anur, P, Yu, K, Tarabichi, M, Deshwar, A, Wintersinger, J, Kleinheinz, K, Vázquez-García, I, Haase, K, Jerman, L, Sengupta, S, Macintyre, G, Malikic, S, Donmez, N, Livitz, DG, Cmero, M, Demeulemeester, J, Schumacher, S, Fan, Y, Yao, X, Lee, J, Schlesner, M, Boutros, PC, Bowtell, DD, Zhu, H, Getz, G, Imielinski, M, Beroukhim, R, Sahinalp, SC, Ji, Y, Peifer, M, Markowetz, F, Mustonen, V, Yuan, K, Wang, W, Morris, QD, Spellman, PT, Wedge, DC, Van Loo, P & PCAWG Consortium 2020, 'The evolutionary history of 2,658 cancers', Nature, vol. 578, no. 7793, pp. 122-128. https://doi.org/10.1038/s41586-019-1907-7

TY - JOUR

T1 - The evolutionary history of 2,658 cancers

AU - PCAWG Evolution & Heterogeneity Working Group

AU - Gerstung, Moritz

AU - Jolly, Clemency

AU - Leshchiner, Ignaty

AU - Dentro, Stefan C

AU - Gonzalez, Santiago

AU - Rosebrock, Daniel

AU - Mitchell, Thomas J

AU - Rubanova, Yulia

AU - Anur, Pavana

AU - Yu, Kaixian

AU - Tarabichi, Maxime

AU - Deshwar, Amit

AU - Wintersinger, Jeff

AU - Kleinheinz, Kortine

AU - Vázquez-García, Ignacio

AU - Haase, Kerstin

AU - Jerman, Lara

AU - Sengupta, Subhajit

AU - Macintyre, Geoff

AU - Malikic, Salem

AU - Donmez, Nilgun

AU - Livitz, Dimitri G

AU - Cmero, Marek

AU - Demeulemeester, Jonas

AU - Schumacher, Steven

AU - Fan, Yu

AU - Yao, Xiaotong

AU - Lee, Juhee

AU - Schlesner, Matthias

AU - Boutros, Paul C

AU - Bowtell, David D

AU - Zhu, Hongtu

AU - Getz, Gad

AU - Imielinski, Marcin

AU - Beroukhim, Rameen

AU - Sahinalp, S Cenk

AU - Ji, Yuan

AU - Peifer, Martin

AU - Markowetz, Florian

AU - Mustonen, Ville

AU - Yuan, Ke

AU - Wang, Wenyi

AU - Morris, Quaid D

AU - Spellman, Paul T

AU - Wedge, David C

AU - Van Loo, Peter

AU - PCAWG Consortium

AU - Lynch, Andy

PY - 2020/2

Y1 - 2020/2

N2 - 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.

AB - 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.

KW - DNA Repair/genetics

KW - Evolution, Molecular

KW - Gene Dosage

KW - Genes, Tumor Suppressor

KW - Genetic Variation

KW - Genome, Human/genetics

KW - Humans

KW - Mutagenesis, Insertional/genetics

KW - Neoplasms/genetics

U2 - 10.1038/s41586-019-1907-7

DO - 10.1038/s41586-019-1907-7

M3 - Article

C2 - 32025013

SN - 0028-0836

VL - 578

SP - 122

EP - 128

JO - Nature

JF - Nature

IS - 7793

ER -

The evolutionary history of 2,658 cancers

Abstract

Keywords

UN SDGs

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