The evolutionary history of 2,658 cancers

By Moritz Gerstung, Clemency Jolly, I. Leshchiner, S. Dentro, Santiago Gonzalez, T. Mitchell, Yulia Rubanova, Pavana Anur, K. Yu, M. Tarabichi and 60 more. Nature, 2017

937 citations recorded by the source corpus.

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. 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.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/d5c53b6e55188d0d4e3702a51b269f4d94248c1d

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Citations in the corpus

Targeting PI3K/Akt signal transduction for cancer therapy (2021, background): “colon cancer.(11) In contrast to PIK3CA, transforming mutations in the PIK3CB gene are rare; however, the gene is ubiquitously expressed, probably due to the distinct mode of interaction between this isoform and regulatory subunits.”
Genomic basis for RNA alterations in cancer (2020, methodology): “5 and 6 were produced using the RTsne package 68 (with a perplexity value of 3) based on the Pearson correlation of the aggregated expression (log + 1) of the 1,500 most variable genes.”