Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project.
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Authors
Ní Leathlobhair, M
Frangou, A
Kinnersley, B
Cornish, AJ
Chubb, D
Lakatos, E
Arumugam, P
Gruber, AJ
Law, P
Tapinos, A
Jakobsdottir, GM
Peneva, I
Sahli, A
Smyth, EM
Ball, RY
Sylva, R
Benes, K
Stark, D
Young, RJ
Lee, ATJ
Wolverson, V
Houlston, RS
Sosinsky, A
Protheroe, A
Murray, MJ
Wedge, DC
Verrill, C
Testicular Cancer Genomics England Clinical Interpretation Partnership Consortium,
Genomics England Research Consortium,
Frangou, A
Kinnersley, B
Cornish, AJ
Chubb, D
Lakatos, E
Arumugam, P
Gruber, AJ
Law, P
Tapinos, A
Jakobsdottir, GM
Peneva, I
Sahli, A
Smyth, EM
Ball, RY
Sylva, R
Benes, K
Stark, D
Young, RJ
Lee, ATJ
Wolverson, V
Houlston, RS
Sosinsky, A
Protheroe, A
Murray, MJ
Wedge, DC
Verrill, C
Testicular Cancer Genomics England Clinical Interpretation Partnership Consortium,
Genomics England Research Consortium,
Document Type
Journal Article
Date
2024-10-26
Date Accepted
2024-10-03
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.
Citation
Nature Communications, 2024, 15 (1), pp. 9247 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Cancer Genomics