Evidence map›Paper›PMID 26097884›Full record

ArticleOncoscience2015

Methylation changes in the TFAP2E promoter region are associated with BRAF mutation and poorer overall & disease free survival in colorectal cancer.

Andrew D Beggs, Mark P Dilworth, Enric Domingo, Rachel Midgley, David Kerr, Ian P M Tomlinson, Gary W Middleton

Open access · diamondAbstract read
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In one paragraph

Article in Oncoscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 24% 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, 1 synthesis or guideline pooled it, 12 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

7 authors at 3 institutions in 1 country.

Andrew D BeggsTranslational Surgical Biology Laboratory, School of Cancer Sciences, University of Birmingham, Birmingham, UK.
Mark P DilworthTranslational Surgical Biology Laboratory, School of Cancer Sciences, University of Birmingham, Birmingham, UK.
Enric DomingoMolecular & Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Rachel MidgleyDepartment of Oncology, University of Oxford, Oxford, UK.
David KerrDepartment of Oncology, University of Oxford, Oxford, UK.
Ian P M TomlinsonMolecular & Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Gary W MiddletonSchool of Cancer Sciences, University of Birmingham, Birmingham, UK.
University of Birmingham · GBUniversity of Oxford · GBCentre for Human Genetics · GB

Funding

Cancer Research UK 16459Medical Research Council MR/M009157/1
6 · The paper itself

Abstract

introductionBRAF mutant colorectal cancer carries a poor prognosis which is thought to be related to poor response to conventional chemotherapy. BRAF mutation is associated with the serrated tumour phenotype. We hypothesised that one of the mechanisms by which BRAF mutant colorectal cancer demonstrate poor outcomes with chemotherapy is abnormal gene methylation.

methodsThe Cancer Genome Atlas (TCGA) methylation data was analysed using a linear regression model with BRAF mutation as an independent variable. Expression datasets were also obtained to correlate functional changes. Top differentially methylated probes were taken forward for validation by methylation pyrosequencing. These probes were analysed on a cohort of patients enriched for BRAF mutations taken from the VICTOR and QUASAR2 studies.

resultsIn an analysis of 91 tumours (9 BRAF mutant, 82 wild type), the Illumina probe cg11835197 was the probe identified as top differentially methylated (p = 2.56×10-7, Bayes Factor (BF) =6.54). This probe covered a region -413bp from the promoter region of TFAP2E. We found a complex pattern of CpG specific methylation of this region which was associated with both overall (p=0.044) and disease free (p=0.046) survival. DISCUSSION: BRAF mutant tumours may attain part of their chemoresistance from abnormal TFAP2E methylation, which has not previously been described.

Indexed as

BRAF mutationchemoresistanceTFAP2EWnt signalling

Identifiers

PMID26097884
PMCPMC4468337
OpenAlexW2187706676

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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.