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Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach

R. Cortez Cardoso Penha, A. Sexton Oates, S. Senkin, HA. Park, J. Atkins, I. Holcatova, A. Hornakova, S. Savic, S. Ognjanovic, B. Świątkowska, J. Lissowska, D. Zaridze, A. Mukeria, V. Janout, A. Chabrier, V. Cahais, C. Cuenin, G. Scelo, M. Foll,...

. 2024 ; 20 (12) : 1282-1302. [pub] 20241126

Language English Country Germany

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc25003142

Grant support
GeniLuc2017-1-TABAC-03-CIRC-1-[TABAC17-022] Institut National Du Cancer (INCa)
U01CA155309 HHS | National Institutes of Health (NIH)
U01 CA155309 NCI NIH HHS - United States
C98/A24032 Cancer Research UK (CRUK)
001 World Health Organization - International

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.

References provided by Crossref.org

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