Åke Borg
Principal investigator
The evolutionary history of 2,658 cancers
Author
Other contributions
- Åke Borg
- Markus Ringnér
- Johan Staaf
Summary, in English
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.
Department/s
- LUCC: Lund University Cancer Centre
- Familial Breast Cancer
- Breastcancer-genetics
- Molecular Cell Biology
- Breast/lungcancer
- Division of Translational Cancer Research
- Research Group Lung Cancer
Publishing year
2020-02
Language
English
Pages
122-128
Publication/Series
Nature
Volume
578
Issue
7793
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Medical Genetics
Keywords
- DNA Repair/genetics
- Evolution, Molecular
- Gene Dosage
- Genes, Tumor Suppressor
- Genetic Variation
- Genome, Human/genetics
- Humans
- Mutagenesis, Insertional/genetics
- Neoplasms/genetics
Status
Published
Research group
- Familial Breast Cancer
- Research Group Lung Cancer
ISBN/ISSN/Other
- ISSN: 0028-0836