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Genomic landscape of adult testicular germ cell tumours in the 100,000 genomes project
M, N. L. Frangou, A. Kinnersley, B. Cornish, A. J. Chubb, D. Lakatos, E. Arumugam, P. Gruber, A. J. Law, P. Tapinos, Avraam
M, N. L.
Frangou, A.
Kinnersley, B.
Cornish, A. J.
Chubb, D.
Lakatos, E.
Arumugam, P.
Gruber, A. J.
Law, P.
Tapinos, Avraam
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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.
Authors
M, N. L.
Frangou, A.
Kinnersley, B.
Cornish, A. J.
Chubb, D.
Lakatos, E.
Arumugam, P.
Gruber, A. J.
Law, P.
Tapinos, Avraam
Jakobsdottir, Maria G
Peneva, I.
Sahli, Atef
Smyth, E. M.
Ball, R. Y.
Sylva, R.
Benes, K.
Stark, D.
Young, R. J.
Lee, Alexander T J
Wolverson, V.
Houlston, R. S.
Sosinsky, A.
Protheroe, A.
Murray, M. J.
Wedge, David C
Verrill, C.
Frangou, A.
Kinnersley, B.
Cornish, A. J.
Chubb, D.
Lakatos, E.
Arumugam, P.
Gruber, A. J.
Law, P.
Tapinos, Avraam
Jakobsdottir, Maria G
Peneva, I.
Sahli, Atef
Smyth, E. M.
Ball, R. Y.
Sylva, R.
Benes, K.
Stark, D.
Young, R. J.
Lee, Alexander T J
Wolverson, V.
Houlston, R. S.
Sosinsky, A.
Protheroe, A.
Murray, M. J.
Wedge, David C
Verrill, C.
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Date
2024
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Article
Citation
M NL, Frangou A, Kinnersley B, Cornish AJ, Chubb D, Lakatos E, et al. Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project. Nature communications. 2024 Oct 26;15(1):9247. PubMed PMID: 39461959. Pubmed Central PMCID: PMC11513037 Social Care and was created in 2013 to introduce WGS into healthcare in conjunction with NHS England. Authors affiliated with Genomics England are, or were, salaried by or seconded to Genomics England (A. Sosinsky, P.A.) or act as a GeCIP-specific patient/participant representative (V.W.). All other authors declare they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Epub 2024/10/27. eng.