Evidence map›Paper›PMID 39824946›Full record

ArticleOncogene2025

Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.

Sabrina H Rossi, Victoria Dombrowe, Laura Godfrey, Teodora Bucaciuc Mracica, Sara Pita, Toby Milne-Clark, Justicia Kyeremeh, Gahee Park, Christopher G Smith, Radoslaw P Lach and 6 more

Abstract read
In one paragraph

Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

16 authors.

Sabrina H RossiEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK. Sr725@cam.ac.uk.ORCID http://orcid.org/0000-0001-7048-7158
Victoria DombroweInstitute for Computational Cancer Biology (ICCB), Centre for Integrated Oncology (CIO), Cancer Research Centre Cologne Essen (CCCE), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Laura GodfreyInstitute for Computational Cancer Biology (ICCB), Centre for Integrated Oncology (CIO), Cancer Research Centre Cologne Essen (CCCE), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0003-2393-9881
Teodora Bucaciuc MracicaInstitute for Computational Cancer Biology (ICCB), Centre for Integrated Oncology (CIO), Cancer Research Centre Cologne Essen (CCCE), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Sara PitaEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.
Toby Milne-ClarkEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.
Justicia KyeremehDepartment of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0009-0008-1477-7829
Gahee ParkEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.
Christopher G SmithCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Radoslaw P LachEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.
Anne BabbageEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.
Anne Y WarrenCRUK Cambridge Centre, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Thomas J MitchellEarly Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-0761-9503
Grant D Stewart *Department of Surgery, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-3188-9140
Roland Schwarz *Institute for Computational Cancer Biology (ICCB), Centre for Integrated Oncology (CIO), Cancer Research Centre Cologne Essen (CCCE), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.ORCID http://orcid.org/0000-0001-9155-4268
Charlie E Massie *Early Cancer Institute, Cancer Research UK Cambridge Centre, Cambridge Biomedical Campus, Cambridge, UK.ORCID http://orcid.org/0000-0003-2314-4843

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples. We perform a comprehensive systematic analysis of heterogeneity between patients, within a patient and within a sample. We demonstrate that bulk methylation data may be deconvoluted into cell-type-specific latent methylation components (LMCs), and that LMC1, which is likely to represent T cells, is associated with prognostic parameters. Differential epipolymorphism was noted between ccRCC and normal tissue in the promoter region of genes which are known to be associated with kidney cancer. This was externally validated in an independent cohort of 71 ccRCC and normal kidney tissues. Differential epipolymorphism in the gene promoter was a predictor of gene expression, after adjusting for average methylation. This represents the first evaluation of epipolymorphism in ccRCC and suggests that gains and losses in methylation disorder may have a functional relevance, gleaning important information on tumourigenesis.

Indexed as

Carcinoma, Renal CellDNA MethylationEpigenesis, GeneticKidney NeoplasmsAgedExome SequencingFemaleGene Expression Regulation, NeoplasticGenetic HeterogeneityHumansMaleMiddle AgedPrognosisPromoter Regions, Genetic

Identifiers

PMID39824946
PMCPMC11976292

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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.