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

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.

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Publication Details

Journal
Nature Communications
Published
2024-10-26
DOI
https://doi.org/10.1038/s41467-024-53193-6
Citations
16
Primary Topic
Cancer Genomics and Diagnostics
Type
article
Field-Weighted Citation Impact
4.56

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article

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

Máire Ní Leathlobhair, David C. Wedge, Alexander T.J. Lee, Ksenija Benes et al.
16 citations
Nature Communications
Cancer Genomics and Diagnostics
4.56
article

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

Máire Ní Leathlobhair, David C. Wedge, Alexander T.J. Lee, Ksenija Benes, G. Maria Jakobsdottir, Richard S. Houlston, Andreas Gruber, Avraam Tapinos, Richard Y. Ball, Iliana Peneva, Atef Sahli, Philip Law, Alex J. Cornish, Andrew Protheroe, Alona Sosinsky, Eszter Lakatos, Ben Kinnersley, Matthew Jonathan Murray, Dan Stark, Clare Verrill, Anna Frangou, Daniel Chubb, Prabhu Arumugam, Robin Young, E.G. Smyth, Rushan Sylva, Vincent Wolverson
article en
16 citations

Abstract

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.

Nature CommunicationsVol. 15(1)
University of Leeds (GB), Institute of Cancer Research (GB), University of Konstanz (DE), Guy's and St Thomas' NHS Foundation Trust (GB), Trinity College Dublin (IE), University of Cambridge (GB), Manchester Academic Health Science Centre (GB), Norfolk and Norwich University Hospitals NHS Foundation Trust (GB), St James's University Hospital (GB), Nuffield Orthopaedic Centre (GB), Cambridge University Hospitals NHS Foundation Trust (GB), Weston Park Cancer Centre (GB), Open Data Institute (GB), University of Manchester (GB), University of Oxford (GB), Sheffield Teaching Hospitals NHS Foundation Trust (GB), Ludwig Cancer Research (GB), Cancer Research UK Manchester Institute (GB), The Christie Hospital (GB), The Christie NHS Foundation Trust (GB), Genomics England (GB), Oxford BioMedica (United Kingdom) (GB), Oxford University Hospitals NHS Trust (GB), CRUK Lung Cancer Centre of Excellence (GB), The Royal Wolverhampton NHS Trust (GB), Max Planck Institute of Molecular Cell Biology and Genetics (DE), University College London (GB), Chalmers University of Technology (SE), University of Gothenburg (SE)
Wellcome Trust, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, Manchester Biomedical Research Centre, Medical Research Council, NIHR Oxford Biomedical Research Centre
Openalex Percentile: Top 4%
Cancer Genomics and Diagnostics
4.56
DOIOpen Access PDFOpenAlex
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