Analysis of 10,478 cancer genomes identifies candidate driver genes and opportunities for precision oncology
Open accessPublished version of a preprint
Abstract
Tumor genomic profiling is increasingly seen as a prerequisite to guide the treatment of patients with cancer. To explore the value of whole-genome sequencing (WGS) in broadening the scope of cancers potentially amenable to a precision therapy, we analysed whole-genome sequencing data on 10,478 patients spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 candidate driver genes, including 74 that are new to any cancer. We estimate that approximately 55% of patients studied harbor at least one clinically relevant mutation, predicting either sensitivity or resistance to certain treatments or clinical trial eligibility. By performing computational chemogenomic analysis of cancer mutations we identify additional targets for compounds that represent attractive candidates for future clinical trials. This study represents one of the most comprehensive efforts thus far to identify cancer driver genes in the real world setting and assess their impact on informing precision oncology.
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- Authors
- Kinnersley, B., Sud, A., Everall, A., Cornish, A. J., Chubb, D., Culliford, R., Gruber, A. J., Lärkeryd, A., Mitsopoulos, C., Wedge, D., & Houlston, R.
- Affiliations
- Institute of Cancer Research (GB)
- Broad Institute (US)
- University of Konstanz (DE)
- University of Manchester (GB)
- Corresponding author
- Houlston, Richard
- ORCID
- Venue
- Nature Genetics
- Published
- 2024-06-18
- Volume
- 56
- Issue
- 9
- Pages
- 1868-1877
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC11387197
- OpenAlex
- W4399781527
- Cited by
- 73
- References
- 11
- Citations by year
- 2026: 30 · 2025: 35 · 2024: 8
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Genetics (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- KOPS (University of Konstanz) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (214388, 227000/Z/23/Z)
- Cancer Research UK (C1298/A8362)
- DH | National Institute for Health Research
- Academy of Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- cancer driver genes, precision oncology, whole genome sequencing, tumor genomic profiling, 100,000 Genomes Project, chemogenomics, drug target identification, inclusion and exclusion criteria, somatic mutations
- MeSH terms
- Whole Genome Sequencing, Humans, Medical Oncology, Mutation, Neoplasms, Genome, Human, Genomics, Precision Medicine
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