Journal Article

The evolutionary history of 2,658 cancers

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

2020

Overview

Cancer develops through a process of somatic evolution 1 , 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 processes 3 . 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. Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45/23 / 631/114 / 631/181/735 / 631/67/69 / 692/699/67/69 / Basic Medicine / Biological evolution / Biopsy / Cancer / Chromosomes / Consortia / Copy number / DNA Repair - genetics / Evolution / Evolution, Molecular / Evolutionary biology / Evolutionary genetics / Gene Dosage / Gene sequencing / Genes / Genes, Tumor Suppressor / Genetic aspects / Genetic Variation / Genome, Human - genetics / Genomes / Genomic instability / Glioblastoma / Humanities and Social Sciences / Humans / Identification and classification / Life history / Medical and Health Sciences / Medical Genetics and Genomics (including Gene Therapy) / Medicin och hälsovetenskap / Medicinsk genetik och genomik (Här ingår: Genterapi) / Medicinska och farmaceutiska grundvetenskaper / Medulloblastoma / multidisciplinary / Mutagenesis, Insertional - genetics / Mutation / Natural history / Neoplasms - genetics / Science / Science (multidisciplinary) / Trisomy / Tumorigenesis / Tumors / Whole genome sequencing