2026
Comprehensive repertoire of the chromosomal alteration and mutational signatures across 16 cancer types
Everall A, Tapinos A, Hawari A, Cornish AJ, Sud A, Chubb D, Kinnersley B, Frangou A, Barquin M, Jung J, Church DN, Alexandrov LB, Houlston RS, Gruber AJ, Wedge DC.
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- Everall A — Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
- Tapinos A — Manchester Cancer Research Centre, University of Manchester, Manchester, UK.
- Hawari A — Manchester Cancer Research Centre, University of Manchester, Manchester, UK.
- Cornish AJ — Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
- Sud A — Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
- Chubb D — Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
- Kinnersley B — Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.
- Frangou A — Nuffield Department of Medicine, Big Data Institute, University of Oxford, Oxford, UK.
- Barquin M — Department of Biology, University of Konstanz, Konstanz, Germany.
- Jung J — Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK.
- Church DN — Oxford NIHR Comprehensive Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
- Alexandrov LB — Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
- Houlston RS — Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. richard.houlston@icr.ac.uk.
- Gruber AJ — Department of Biology, University of Konstanz, Konstanz, Germany. gruber@uni-konstanz.de.
- Wedge DC — Manchester Cancer Research Centre, University of Manchester, Manchester, UK. david.wedge@manchester.ac.uk.
Whole-genome sequencing (WGS) enables exploration of the full spectrum of oncogenic processes that generate characteristic patterns of mutations. Mutational signatures provide clues to tumor etiology and highlight potentially targetable pathway defects. Here alongside single-base substitution, doublet-base substitution, small insertion and deletion and copy number aberration signatures previously covered by the Catalogue of Somatic Mutations in Cancer (COSMIC), we report signatures from an additional mutation type, structural variations (SVs), extracted de novo from WGS in 10,983 patients across 16 tumor types recruited to the 100,000 Genomes Project. Across the five mutation classes, we report 134 signatures, 26 of which are new to COSMIC, including an SV signature reference set. By relating signatures to genomic features and clinical phenotypes, we provide further insights into mutagenic processes and the application of signature analysis to precision oncology.
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