Clonal status of actionable driver events and the timing of mutational processes in cancer evolution
Cancer Research UK · University College London · +4 more institutions
Abstract
Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and…
Citation impact
- FWCI
- 26.89
- Percentile
- 100%
- References
- 45
Authors
6- NMNicholas McGranahanCorresponding
Cancer Research UK, University College London
- FFFrancesco Favero
Technical University of Denmark
- ECElza C. de Bruin
CRUK Lung Cancer Centre of Excellence, University College London
- NJNicolai J. BirkbakCorresponding
Cancer Research UK, CRUK Lung Cancer Centre of Excellence, University College London, Technical University of Denmark
- ZSZoltán Szállási
Boston Children's Hospital, Harvard University, Technical University of Denmark
Topics & keywords
- Somatic evolution in cancer
- Biology
- Cancer
- Genetics
- Medicine
- Computational biology
- Bioinformatics