Evidence map›Paper›PMID 23671423›Full record

ArticlePLoS genetics2013

Loss of expression and promoter methylation of SLIT2 are associated with sessile serrated adenoma formation.

Andrew D Beggs, Angela Jones, Neil Shepherd, Abed Arnaout, Caroline Finlayson, A Muti Abulafi, Dion G Morton, Glenn M Matthews, Shirley V Hodgson, Ian P M Tomlinson

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Candidate predisposing germline copy number variants in early onset colorectal cancer patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017
    Article
  8. Article
  9. Article
  10. Article
  11. Observational
  12. Maintaining the unmethylated state.Clinical epigenetics · 2013
    Article
  13. Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer.International journal of clinical and experimental pathology · 2013
    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

10 authors at 6 institutions in 1 country.

Andrew D BeggsMolecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. abeggs@well.ox.ac.uk
Angela Jones
Neil Shepherd
Abed Arnaout
Caroline Finlayson
A Muti Abulafi
Dion G Morton
Glenn M Matthews
Shirley V Hodgson
Ian P M Tomlinson
Croydon University Hospital · GBUniversity of Birmingham · GBUniversity of Oxford · GBCheltenham General Hospital · GBSt George's Hospital · GBSt George's, University of London · GB

Funding

Cancer Research UK 16459Department of Health 11/100/29Department of Health EME/11/100/29Wellcome Trust 090532Wellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

Serrated adenomas form a distinct subtype of colorectal pre-malignant lesions that may progress to malignancy along a different molecular pathway than the conventional adenoma-carcinoma pathway. Previous studies have hypothesised that BRAF mutation and promoter hypermethylation plays a role, but the evidence for this is not robust. We aimed to carry out a whole-genome loss of heterozygosity analysis, followed by targeted promoter methylation and expression analysis to identify potential pathways in serrated adenomas. An initial panel of 9 sessile serrated adenomas (SSA) and one TSA were analysed using Illumina Goldengate HumanLinkage panel arrays to ascertain regions of loss of heterozygosity. This was verified via molecular inversion probe analysis and microsatellite analysis of a further 32 samples. Methylation analysis of genes of interest was carried out using methylation specific PCR (verified by pyrosequencing) and immunohistochemistry used to correlate loss of expression of genes of interest. All experiments used adenoma samples and normal tissue samples as control. SSA samples were found on whole-genome analysis to have consistent loss of heterozygosity at 4p15.1-4p15.31, which was not found in the sole TSA, adenomas, or normal tissues. Genes of interest in this region were PDCH7 and SLIT2, and combined MSP/IHC analysis of these genes revealed significant loss of SLIT2 expression associated with promoter methylation of SLIT2. Loss of expression of SLIT2 by promoter hypermethylation and loss of heterozygosity events is significantly associated with serrated adenoma development, and SLIT2 may represent a epimutated tumour suppressor gene according to the Knudson "two hit" hypothesis.

Indexed as

AdenomaAdultAgedAged, 80 and overColorectal NeoplasmsDNA MethylationFemaleGene Expression Regulation, NeoplasticGenetic LinkageHumansIntercellular Signaling Peptides and ProteinsLoss of HeterozygosityMaleMiddle AgedNerve Tissue ProteinsSlit Homolog 2 ProteinIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsSlit Homolog 2 Protein

Identifiers

PMID23671423
PMCPMC3649993
OpenAlexW2029575827

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.