A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation.
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s12885-023-11162-0.pdf
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2.88 MB
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Resource type
Journal article
Date published
August 1, 2023
Abstract
SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of DNA methylation. is frequently mutated in cancer, however, the functional impact of loss and depletion on DNA methylation across cancer types and tumorigenesis is currently unknown. Here, we perform a pan-cancer analysis and show that both mutation and reduced expression are associated with DNA methylation dysregulation across 21 out of the 24 cancer types tested. In renal cancer, these DNA methylation changes are associated with altered gene expression of oncogenes, tumour suppressors, and genes involved in neoplasm invasiveness, including , and . This suggests a new role for loss in tumorigenesis and cancer aggressiveness through DNA methylation dysregulation. Moreover, using a robust machine learning methodology, we develop and validate a 3-CpG methylation signature which is sufficient to predict mutation status with high accuracy and correlates with patient prognosis.
Funder
| Funder name | Awards |
Clarendon Fund, United Kingdom | |
Cancer Research UK, United Kingdom | Project CBIG:23969 |
H2020 Excellent Science, European Union | Project ‘CETOCOEN Excellence’ (857560) |
Wellcome Trust, United Kingdom | Intermediate Clinical Fellowship to B.P.F. (no. 201488/Z/16/Z) |
Kyoto University, Japan | |
European Research Council, European Union | Project MICROC:772970 |
Medical Research Council, United Kingdom | MC_PC_12003 |
UK Research and Innovation, United Kingdom | Grant number: MC_PC_12003 |
Journal title
BMC Cancer
Volume
23
Article number
721
Publisher
Springer Science and Business Media LLC
Place of publication
Berlin/Heidelberg, Germany
eISSN
1471-2407
Date accepted
July 7, 2023
Official URL
Rights statement
In Copyright
Additional information
IF = 4.638 (2022-2023)