Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer

  title={Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer},
  author={Pooneh Mokarram and M. Zamani and Soudabeh Kavousipour and Fakhraddin Naghibalhossaini and Cambyz Irajie and Mostafa Moradi Sarabi and Seyed Vahid Hosseini},
  journal={Molecular Biology Reports},
Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal cancer incidence differs widely among different geographic regions. In addition to mutational changes, epigenetic mechanisms also play important roles in the pathogenesis of CRCs. O6-methylguanine-DNA methyltransferase (O6-MGMT) is a DNA repair protein and in the absence of MGMT activity, G-to-A transition may accumulate in the specific genes such as K-ras and p53. To identify which CpG sites are critical for its… 

O6-Methyguanine-DNA Methyl Transferase (MGMT) Promoter Methylation in Serum DNA of Iranian Patients with Colorectal Cancer

MGMT hypermethylation can be detected in free circulating DNA in serum of CRC patients and can be used “as a clinical biomarker” for early diagnosis and prognostic assessment of the disease.

Methylation in Colorectal Cancer

The aim has been to define the molecular profiles including patterns of hypermethylation of the most important cancer candidate genes, polymorphism and mutation of specific genes in CRC in studies, with relatively different environmental and genetic factors compared to Western countries.

Clinicopathological significance and potential drug target of O6-methylguanine-DNA methyltransferase in colorectal cancer: a meta-analysis

The results of this meta-analysis suggest that MGMT hypermethylation is associated with an increased risk and high levels of MSI and may play an important role in CRC initiation, as well as having limited value in prediction of prognosis in CRC patients.

Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps.

Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision and might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition.

Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review

MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade, however, MGMTmethylation is not associated with the prognosis of CRC.

APC2 and CYP1B1 methylation changes in the bone marrow of acute myeloid leukemia patients during chemotherapy.

CYP1B1 promoter methylation was induced during chemotherapy, whereas the APC2 promoter remained hemimethylated, and the changes in CYP1B 1 methylation were dependent on the AML subtypes and the gender of the patients.

Prognostic impact of MGMT promoter methylation and MGMT and CD133 expression in colorectal adenocarcinoma

The hypothesis that MGMT expression may be an OS biomarker as useful as tumor stage or differentiation grade and that CD133expression may be a predictive biomarker of DFS is supported.

Polyunsaturated fatty acids and DNA methylation in colorectal cancer

Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids (PUFAs) in preventing CRC and recent investigations linking PUFAs and DNA methylation-associated CRC risk are summarized.

Induction of Epigenetic Alteration by CPUK02, An Ent- kaurenoid Derivative of Stevioside

Positive correlation was found between mRNA expression of DNMT3b and gene promoter hypermethylation after treatment with CPUK02 and 5-AZA and it was confirmed thatCPUK02 like 5- AZA exhibits demethylating properties.



Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia.

The presence of aberrant hypermethylation was associated with loss of MGMT protein, in contrast to retention of protein in the majority of tumors without aberrantHypermethylation, suggesting that epigenetic inactivation of MG MT plays an important role in primary human neoplasia.

Promoter methylation status of the MGMT, hMLH1, and CDKN2A/p16 genes in non-neoplastic mucosa of patients with and without colorectal adenomas.

The methylation status of these genes in rectal mucosa biopsies detected by MSP assays may not distinguish between patients with and without adenomas in the colon, and methylated alleles of the hMLH1 and MGMT genes were frequently detected in normal rectal membranes, while the frequency of CDKN2A/p16 methylation detected was very low.

O6-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions

The findings provide good evidence to show that MGMT changes, including methylation, are selected rather than background events, at least in some cases, and probably has a weak or moderate effect on the mutation spectrum in colorectal cancers.

Comethylation of p16 and MGMT genes in colorectal carcinoma: correlation with clinicopathological features and prognostic value.

It is suggested that comethylation of promoters of p16 and MGMT genes could have a prognostic value in patients with CRC and concurrent methylation of both genes correlates with better prognosis.

MGMT promoter methylation and field defect in sporadic colorectal cancer.

Some colorectal cancers arise from a field defect defined by epigenetic inactivation of MGMT, and detection of this abnormality may ultimately be useful in risk assessment for coloreCTal cancer.

Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status.

It is concluded that high concentrations of serum folate/vitamin B(12) levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes.

Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients.

The results suggest an association between tobacco smoking and an increased incidence of aberrant promoter methylation of the p16 and MGMT genes in non-small cell lung cancer.

High Frequency of Genes’ Promoter Methylation, but Lack of BRAF V600E Mutation among Iranian Colorectal Cancer Patients

A distinct molecular pathway for methylation of APC2, p14, and ECAD genes from those previously described for colorectal cancers with BRAF or KRAS mutations is suggested.

Distinct High-Profile Methylated Genes in Colorectal Cancer

A significantly higher methylation rate was found for GPNMB, ICAM5, and CHD5 genes in AA patients compared to Iranians, suggesting these genes might play a role in the high incidence and aggressiveness of CRC in the AA population.