| Autor: |
Máire Ní Leathlobhair, Anna Frangou, Ben Kinnersley, Alex J. Cornish, Daniel Chubb, Eszter Lakatos, Prabhu Arumugam, Andreas J. Gruber, Philip Law, Avraam Tapinos, G. Maria Jakobsdottir, Iliana Peneva, Atef Sahli, Evie M. Smyth, Richard Y. Ball, Rushan Sylva, Ksenija Benes, Dan Stark, Robin J. Young, Alexander T. J. Lee, Vincent Wolverson, Richard S. Houlston, Alona Sosinsky, Andrew Protheroe, Matthew J. Murray, David C. Wedge, Clare Verrill, Testicular Cancer Genomics England Clinical Interpretation Partnership Consortium, Genomics England Research Consortium |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-13 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-53193-6 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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