| Autor: |
Ricardo Cortez Cardoso Penha, Alexandra Sexton Oates, Sergey Senkin, Hanla A Park, Joshua Atkins, Ivana Holcatova, Anna Hornakova, Slavisa Savic, Simona Ognjanovic, Beata Świątkowska, Jolanta Lissowska, David Zaridze, Anush Mukeria, Vladimir Janout, Amelie Chabrier, Vincent Cahais, Cyrille Cuenin, Ghislaine Scelo, Matthieu Foll, Zdenko Herceg, Paul Brennan, Karl Smith-Byrne, Nicolas Alcala, James D Mckay |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Systems Biology, Vol 20, Iss 12, Pp 1282-1302 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1744-4292 |
| DOI: |
10.1038/s44320-024-00072-3 |
| Popis: |
Abstract Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial–mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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