Evidence map›Paper›PMID 37528416›Full record

ArticleBMC cancer2023

A role for SETD2 loss in tumorigenesis through DNA methylation dysregulation.

Hira Javaid, Alessandro Barberis, Olga Chervova, Isar Nassiri, Vitaly Voloshin, Yusuke Sato, Seishi Ogawa, Benjamin Fairfax, Francesca Buffa, Timothy C Humphrey

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 8 institutions in 2 countries.

Hira JavaidDepartment of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Alessandro BarberisNuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Olga ChervovaUCL Cancer Institute, University College London, London, WC1E 6DD, UK.
Isar NassiriOxford Genomics Centre, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.
Vitaly VoloshinRoyal Botanic Gardens Kew, Kew Green, Richmond, TW9 3AE, Surrey, UK.
Yusuke SatoDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Seishi OgawaDepartment of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Benjamin FairfaxThe MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital/Headley Way, OX3 9DS, Oxford, UK.
Francesca BuffaDepartment of Oncology, University of Oxford, Oxford, OX3 7DQ, UK.
Timothy C HumphreyDepartment of Oncology, University of Oxford, Oxford, OX3 7DQ, UK. timothy.humphrey@sussex.ac.uk.
Kyoto University · JPUniversity of Oxford · GBCentre for Human Genetics · GBJohn Radcliffe Hospital · GBMRC Weatherall Institute of Molecular Medicine · GBRoyal Botanic Gardens, Kew · GBUniversity College London · GBUniversity of Sussex · GB

Funding

Cancer Research UK 23969Cancer Research UK CBIG:23969European Research Council project MICROC:772970Medical Research Council MC_PC_12003Medical Research Council MR/X006778/1Medical Research Council MR/X006778/2Wellcome Trust
6 · The paper itself

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.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsCarcinogenesisCell Transformation, NeoplasticDNA MethylationHistonesHumansHistonesDNA methylationH3K36me3Machine learning biomarkerRenal cancer biomarkerSETD2

Identifiers

PMID37528416
PMCPMC10394884
OpenAlexW4385462147

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.