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 Servi...

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Published in:Nature communications Vol. 15; no. 1; pp. 9247 - 13
Main Authors: Ní Leathlobhair, Máire, Frangou, Anna, Kinnersley, Ben, Cornish, Alex J., Chubb, Daniel, Lakatos, Eszter, Arumugam, Prabhu, Gruber, Andreas J., Law, Philip, Tapinos, Avraam, Jakobsdottir, G. Maria, Peneva, Iliana, Sahli, Atef, Smyth, Evie M., Ball, Richard Y., Sylva, Rushan, Benes, Ksenija, Stark, Dan, Young, Robin J., Lee, Alexander T. J., Wolverson, Vincent, Houlston, Richard S., Sosinsky, Alona, Protheroe, Andrew, Murray, Matthew J., Wedge, David C., Verrill, Clare
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 26.10.2024
Nature Publishing Group
Nature Portfolio
Subjects:
45
45/23
631/114
631/67/1836
631/67/580
631/67/68
631/67/69
Adult
Antigens
Cancer
Copy number
Data analysis
Divergence
DNA Copy Number Variations - genetics
Gene sequencing
Genome, Human
Genomes
Genomic analysis
Genomics
Genomics - methods
Histocompatibility antigen HLA
Humanities and Social Sciences
Humans
Leukocytes
Male
Medical Genetics and Genomics
Medicinsk genetik och genomik
multidisciplinary
Mutation
Neoplasms, Germ Cell and Embryonal - genetics
Neoplasms, Germ Cell and Embryonal - pathology
Pathogenesis
Science
Science (multidisciplinary)
Seminoma
Seminoma - genetics
Seminoma - pathology
Subgroups
Testes
Testicular Neoplasms - genetics
Testicular Neoplasms - pathology
Tumors
Whole Genome Sequencing
United Kingdom > UK
England
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Testicular germ cell tumours (TGCT) are the most common cancers in young men. Here, the authors analyse the genomic landscape of TGCT using data from the Genomics England 100,000 Genomes Project, revealing divergent evolutionary trajectories and the prevalence of human leukocyte antigen loss.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-53193-6