A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation.
dc.contributor.author | Javaid, H | |
dc.contributor.author | Barberis, A | |
dc.contributor.author | Chervova, O | |
dc.contributor.author | Nassiri, I | |
dc.contributor.author | Voloshin, V | |
dc.contributor.author | Sato, Y | |
dc.contributor.author | Ogawa, S | |
dc.contributor.author | Fairfax, B | |
dc.contributor.author | Buffa, F | |
dc.contributor.author | Humphrey, TC | |
dc.date.accessioned | 2024-01-05T15:18:24Z | |
dc.date.available | 2023-07-07 | |
dc.date.available | 2024-01-05T15:18:24Z | |
dc.date.issued | 2023-08-01 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93462 | |
dc.description.abstract | SETD2-dependent H3 Lysine-36 trimethylation (H3K36me3) has been recently linked to the deposition of de-novo DNA methylation. SETD2 is frequently mutated in cancer, however, the functional impact of SETD2 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 SETD2 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 TP53, FOXO1, and CDK4. This suggests a new role for SETD2 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 SETD2 mutation status with high accuracy and correlates with patient prognosis. | en_US |
dc.format.extent | 721 - ? | |
dc.language | eng | |
dc.publisher | Springer Nature | en_US |
dc.relation.ispartof | BMC Cancer | |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Reprints and permissions | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | DNA methylation | en_US |
dc.subject | H3K36me3 | en_US |
dc.subject | Machine learning biomarker | en_US |
dc.subject | Renal cancer biomarker | en_US |
dc.subject | SETD2 | en_US |
dc.subject | Humans | en_US |
dc.subject | DNA Methylation | en_US |
dc.subject | Histones | en_US |
dc.subject | Carcinoma, Renal Cell | en_US |
dc.subject | Kidney Neoplasms | en_US |
dc.subject | Carcinogenesis | en_US |
dc.subject | Cell Transformation, Neoplastic | en_US |
dc.title | A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation. | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2023, the Author(s). Published by Springer Nature | |
dc.identifier.doi | 10.1186/s12885-023-11162-0 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37528416 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 23 | en_US |
dcterms.dateAccepted | 2023-07-07 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
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