ArticleGut2005
O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions.
Article in Gut, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Pooled it
- Hypermethylation ofAdvanced biomedical research · 2023Article
- Genome-wide DNA methylation status of Mongolians exhibits signs of cellular stress response related to their nomadic lifestyle.Journal of physiological anthropology · 2022Article
- Probing altered enzyme activity in the biochemical characterization of cancer.Bioscience reports · 2022Review
- Promoter Methylation of Four Tumor Suppressor Genes in Human Papillary Thyroid Carcinoma.Iranian journal of pathology · 2019Article
- Loss of CDX2 gene expression is associated with DNA repair proteins and is a crucial member of the Wnt signaling pathway in liver metastasis of colorectal cancer.Oncology letters · 2018Article
- Clinical biomarkers for cancer recognition and prevention: A novel approach with optical measurements.Cancer biomarkers : section A of Disease markers · 2018Review
- Mapping clinicopathological entities within colorectal mucinous adenocarcinomas: a hierarchical clustering approach.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- Epigenetic reduction of DNA repair in progression to gastrointestinal cancer.World journal of gastrointestinal oncology · 2015Article
- Methylation of MGMT and ADAMTS14 in normal colon mucosa: biomarkers of a field defect for cancerization preferentially targeting elder African-Americans.Oncotarget · 2015Article
- MGMT gene silencing by promoter hypermethylation in gastric cancer in a high incidence area.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Novel diet-related mouse model of colon cancer parallels human colon cancer.World journal of gastrointestinal oncology · 2014Article
- Tumor-associated mutations in O⁶ -methylguanine DNA-methyltransferase (MGMT) reduce DNA repair functionality.Molecular carcinogenesis · 2014Article
- Splice site and Germline variations of the MGMT gene in Esophageal cancer from Kashmir Valley: India.International journal of health sciences · 2013Article
- Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer.Molecular biology reports · 2013Article
- Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2013Review
- Analysis of O6-methylguanine-DNA methyltransferase methylation status in sporadic colon polyps.Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2012Article
- Distinct profiles of epigenetic evolution between colorectal cancers with and without metastasis.The American journal of pathology · 2011Article
- MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers.Cancer causes & control : CCC · 2011Article
- O6-methylguanine induces altered proteins at the level of transcription in human cells.Nucleic acids research · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsO(6)-methylguanine methyltransferase (MGMT) repairs inappropriately methylated guanine in DNA. MGMT mutations have not previously been reported in cancers, but in colorectal tumours MGMT promoter methylation is common and has been associated with increased G:C>A:T transitions, a high frequency of K-ras mutations, and low level microsatellite instability (MSI low). However, some have suggested that MGMT changes are background or secondary events, with little importance for tumorigenesis.
methodsWe have analysed fresh frozen colorectal cancers and colorectal cancer cell lines for MGMT changes: mutations, allelic loss, and protein expression.
resultsSix of 113 cancers harboured somatic missense MGMT mutations, at least three of which probably caused reduced MGMT function and were accompanied by silencing or loss of the wild-type allele. Cancers with pathogenic MGMT mutations tended to harbour G:C>A:T somatic mutations at other loci. Overall, MGMT expression was reduced or lost in more than half of the cancers. We found no association between MGMT expression and the somatic mutation spectrum at APC, beta-catenin, K-ras, or p53, but decreased MGMT expression was weakly associated with the presence of a G:C>A:T change at any one of these loci. Reduced MGMT expression was not however associated with an increased frequency of K-ras mutations or with MSI low.
conclusionIn summary, we found that mutation of MGMT contributes to decreased protein function. Our findings provide good evidence to show that MGMT changes, including methylation, are selected rather than background events, at least in some cases. Decreased MGMT expression or function probably has a weak or moderate effect on the mutation spectrum in colorectal cancers.
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Registered trials
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.