Evidence map›Paper›PMID 16436636›Full record

ArticleThe Journal of molecular diagnostics : JMD2006

Mutually exclusive promoter hypermethylation patterns of hMLH1 and O6-methylguanine DNA methyltransferase in colorectal cancer.

Edward J Fox, Dermot T Leahy, Robert Geraghty, Hugh E Mulcahy, David Fennelly, John M Hyland, Diarmuid P O'Donoghue, Kieran Sheahan

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of molecular diagnostics : JMD, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
2.3field-weighted citation impact, top 13% 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

19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 46 citations in OpenAlex.

  1. Relationship Between Human mutL Homolog 1 (hMLH1) Hypermethylation and Colorectal Cancer: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2017
    Pooled it
  2. Pooled it
  3. Pooled it
  4. IncreasedMolecular & cellular oncology · 2025
    Article
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  10. Correlation ofOncology letters · 2013
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  14. Article
  15. Review
  16. In vivo biomarkers for targeting colorectal neoplasms.Cancer biomarkers : section A of Disease markers · 2008
    Review
  17. Molecular classification and correlates in colorectal cancer.The Journal of molecular diagnostics : JMD · 2008
    Review
  18. Article
  19. Review
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

8 authors at 2 institutions in 1 country.

Edward J FoxDepartment of Pathology, Conway Institute Of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Dermot T Leahy
Robert Geraghty
Hugh E Mulcahy
David Fennelly
John M Hyland
Diarmuid P O'Donoghue
Kieran Sheahan
St. Vincent's University Hospital · IEUniversity College Dublin · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypermethylation of CpG islands in gene promoter regions is an important mechanism of gene inactivation in cancer. Many cellular pathways, including DNA repair, are inactivated by this type of epigenetic lesion, resulting in proposed mutator phenotypes. Promoter hypermethylation of hMLH1 has been implicated in a subset of colorectal cancers that show microsatellite instability (MSI). Transcriptional silencing of O6-methylguanine DNA methyltransferase (MGMT) has also been described in a variety of neoplasms and has been associated with a consequent mutational spectrum. We investigated the relationship between hMLH1 promoter hypermethylation and MGMT promoter hypermethylation in 110 colorectal cancers using methylation-specific polymerase chain reaction. Expression of hMLH1 and MGMT was assessed by immunohistochemistry. MSI testing was performed using the National Cancer Institute consensus panel of five microsatellite markers. Promoter hypermethylation of hMLH1 was detected in 12% of tumors. This was significantly associated with the MSI-high phenotype (P < 0.01) and loss of hMLH1 expression (P < 0.01). Methylation of the MGMT promoter was detected in 43% of tumors, which were mostly microsatellite stable or MSI-low (P = 0.041) and showed loss of MGMT expression (P < 0.01). We demonstrated an inverse relationship between hMLH1 promoter hypermethylation and MGMT promoter hypermethylation (P = 0.041), suggesting that a number of distinct hypermethylation-associated pathways may exist in colorectal cancer.

Indexed as

DNA MethylationAdaptor Proteins, Signal TransducingAgedCarcinomaCarrier ProteinsColorectal NeoplasmsCpG IslandsFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryMaleMicrosatellite RepeatsMiddle AgedModels, BiologicalMutL Protein Homolog 1Adaptor Proteins, Signal TransducingCarrier ProteinsMLH1 protein, humanMutL Protein Homolog 1Nuclear ProteinsO(6)-Methylguanine-DNA Methyltransferase

Identifiers

PMID16436636
PMCPMC1867561
OpenAlexW1985941947

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.