Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach
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.
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BibTeX
@article{penha2026understanding,
title = {{Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach}},
author = {Ricardo Cortez Cardoso Penha and Alexandra Sexton Oates and Sergey Senkin and Hanla A Park and Joshua Atkins and Ivana Holcatova and Anna Hornakova and Slavisa Savic and Simona Ognjanovic and Beata Świątkowska and Jolanta Lissowska and David Zaridze and Anush Mukeria and Vladimir Janout and Amelie Chabrier and Vincent Cahais and Cyrille Cuenin and Ghislaine Scelo and Matthieu Foll and Zdenko Herceg and Paul Brennan and Karl Smith-Byrne and Nicolas Alcala and James D Mckay},
journal = {Molecular Systems Biology},
year = {2026},
month = oct,
doi = {10.1038/s44320-024-00072-3},
url = {https://hal.science/hal-05842058v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach
AU - Ricardo Cortez Cardoso Penha
AU - Alexandra Sexton Oates
AU - Sergey Senkin
AU - Hanla A Park
AU - Joshua Atkins
AU - Ivana Holcatova
AU - Anna Hornakova
AU - Slavisa Savic
AU - Simona Ognjanovic
AU - Beata Świątkowska
AU - Jolanta Lissowska
AU - David Zaridze
AU - Anush Mukeria
AU - Vladimir Janout
AU - Amelie Chabrier
AU - Vincent Cahais
AU - Cyrille Cuenin
AU - Ghislaine Scelo
AU - Matthieu Foll
AU - Zdenko Herceg
AU - Paul Brennan
AU - Karl Smith-Byrne
AU - Nicolas Alcala
AU - James D Mckay
PY - 2026
DA - 2026/10/28
JO - Molecular Systems Biology
DO - 10.1038/s44320-024-00072-3
UR - https://hal.science/hal-05842058v1
AB - 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.
SN - 1744-4292
SN - 1744-4292
ER -