Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project
Journal article, 2024
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.
Author
Máire Ní Leathlobhair
University of Oxford
Trinity College Dublin
Anna Frangou
Max Planck Society
Ben Kinnersley
University College London (UCL)
Institute of Cancer Research
Alex J. Cornish
Institute of Cancer Research
Daniel Chubb
Institute of Cancer Research
Eszter Lakatos
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Prabhu Arumugam
Genomics England Limited
Andreas J. Gruber
University of Konstanz
Philip Law
Institute of Cancer Research
Avraam Tapinos
University of Manchester
G. Maria Jakobsdottir
Faculty of Biology, Medicine and Health
Health Innovation Manchester
Iliana Peneva
University of Oxford
Atef Sahli
Faculty of Biology, Medicine and Health
University of Oxford
Evie M. Smyth
Trinity College Dublin
Richard Y. Ball
Norfolk and Norwich University Hospital NHS Foundation Trust
Rushan Sylva
Guy's and St Thomas' NHS Foundation Trust
Ksenija Benes
The Royal Wolverhampton NHS Trust
Dan Stark
University of Leeds
Robin J. Young
Weston Park Cancer Centre
Alexander T.J. Lee
Health Innovation Manchester
Vincent Wolverson
Genomics England Limited
Richard S. Houlston
Institute of Cancer Research
Alona Sosinsky
Genomics England Limited
Andrew Protheroe
University of Oxford
Matthew J. Murray
University of Cambridge
Cambridge University Hospitals NHS Foundation Trust
David C. Wedge
Faculty of Biology, Medicine and Health
Health Innovation Manchester
University of Oxford
Clare Verrill
University of Oxford
NIHR Oxford Biomedical Research Centre
Nature Communications
2041-1723 (ISSN) 20411723 (eISSN)
Vol. 15 1 9247Subject Categories (SSIF 2011)
Medical Genetics
DOI
10.1038/s41467-024-53193-6
PubMed
39461959