Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project.

Autor: Ní Leathlobhair M; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. mnileathlobhair@gmail.com.; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK. mnileathlobhair@gmail.com.; Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland. mnileathlobhair@gmail.com., Frangou A; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany., Kinnersley B; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.; University College London Cancer Institute, 72 Huntley Street, London, UK., Cornish AJ; 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., Lakatos E; Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, Gothenburg, Sweden., Arumugam P; Genomics England, London, UK., Gruber AJ; Department of Biology, University of Konstanz, Universitaetsstrasse 10, D-78464, Konstanz, Germany., Law P; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Tapinos A; Manchester Cancer Research Centre, The University of Manchester, Manchester, UK., Jakobsdottir GM; Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Christie Hospital, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Peneva I; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Sahli A; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Smyth EM; Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College Dublin, Dublin, Ireland., Ball RY; Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK., Sylva R; Guy's and St Thomas' NHS Foundation Trust, London, UK., Benes K; Department of Pathology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK., Stark D; Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK., Young RJ; Weston Park Cancer Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK., Lee ATJ; Christie Hospital, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Wolverson V; Genomics England, London, UK., Houlston RS; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Sosinsky A; Genomics England, London, UK., Protheroe A; Department of Oncology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Murray MJ; Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. mjm16@cam.ac.uk.; Department of Pathology, University of Cambridge, Cambridge, UK. mjm16@cam.ac.uk., Wedge DC; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. david.wedge@manchester.ac.uk.; Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. david.wedge@manchester.ac.uk.; Christie Hospital, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. david.wedge@manchester.ac.uk., Verrill C; NIHR Oxford Biomedical Research Centre, Oxford, UK. clare.verrill@ouh.nhs.uk.; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. clare.verrill@ouh.nhs.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 26; Vol. 15 (1), pp. 9247. Date of Electronic Publication: 2024 Oct 26.
DOI: 10.1038/s41467-024-53193-6
Abstrakt: Testicular germ cell tumours (TGCT), which comprise seminoma and non-seminoma subtypes, are the most common cancers in young men. In this study, we present a comprehensive whole genome sequencing analysis of adult TGCTs. Leveraging samples from participants recruited via the UK National Health Service and data from the Genomics England 100,000 Genomes Project, our results provide an extended description of genomic elements underlying TGCT pathogenesis. This catalogue offers a comprehensive, high-resolution map of copy number alterations, structural variation, and key global genome features, including mutational signatures and analysis of extrachromosomal DNA amplification. This study establishes correlations between genomic alterations and histological diversification, revealing divergent evolutionary trajectories among TGCT subtypes. By reconstructing the chronological order of driver events, we identify a subgroup of adult TGCTs undergoing relatively late whole genome duplication. Additionally, we present evidence that human leukocyte antigen loss is a more prevalent mechanism of immune disruption in seminomas. Collectively, our findings provide valuable insights into the developmental and immune modulatory processes implicated in TGCT pathogenesis and progression.
(© 2024. The Author(s).)
Databáze: MEDLINE
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