Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma–carcinoma sequence

  title={Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma–carcinoma sequence},
  author={Kyung‐Hwa Lee and Ji-Shin Lee and Jong Hee Nam and Chan Choi and Min‐Cheol Lee and Chang‐Soo Park and Sang Woo Juhng and Jaehyuk Lee},
  journal={Langenbeck's Archives of Surgery},
PurposeEpigenetic silencing of the DNA mismatch repair genes has been poorly described in colorectal carcinomas showing the classic adenoma–carcinoma pathway of carcinogenesis. The aim of this study was to investigate the methylation status of MutL homolog 1 (hMLH1), MutS homolog 2 (hMSH2), and O-6-methylguanine-DNA methyltransferase (MGMT) in a series of colorectal carcinomas that contain both adenomas and carcinomas.MethodsPromoter methylation of hMLH1, hMSH2, and MGMT was evaluated in normal… 
Expression and promoter methylation status of hMLH1, MGMT, APC, and CDH1 genes in patients with colon adenocarcinoma
The findings suggest that DNA methylation is a useful marker for tumor progression monitoring and that promoter methylation in certain genes is associated with more advanced tumor stage, poor differentiation, and metastasis.
Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens
The hypothesis that DNA methylation in CRC depends from both physiological and environmental factors, with one-carbon metabolism largely involved in this process is supported.
Relationship Between Human mutL Homolog 1 (hMLH1) Hypermethylation and Colorectal Cancer: A Meta-Analysis
A meta-analysis of 45 articles identified a significant association between hMLH1 hypermethylation and colorectal cancer risk using the fixed-effects model and random effects model pooled.
Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients
The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively.
Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer
CDO1 methylation accumulates during the ACS process, and consistently contributes to CRC progression, according to the results of this study.
Absence of hMLH1 or hMSH2 Expression as a Stage-Dependent Prognostic Factor in Sporadic Colorectal Cancers
At initial diagnosis, metastases were found at lower rates in MMR-defective tumors, suggesting MMR status may be a stage-dependent prognostic factor in patients with sporadic colorectal cancer.
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.
Aberrant DNA methylation and epigenetic inactivation of hMSH2 decrease overall survival of acute lymphoblastic leukemia patients via modulating cell cycle and apoptosis.
This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.
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.


Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas.
Methylation analysis of hMLH1, CDKN2A/p16, and MGMT revealed specific methylation profiles for tubular adenomas, tubulovillous/villous adenoma, and colorectal cancers, supporting the use of these alterations in assessment of coloreCTal tumorigenesis.
Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma.
  • J. Herman, A. Umar, S. Baylin
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
The results suggest that microsatellite instability in sporadic colorectal cancer often results from epigenetic inactivation of hMLH1 in association with DNA methylation.
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.
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 hypermethylation of tumor‐related genes in the progression of colorectal neoplasia
The study demonstrated the early and specific involvement of promoter hypermethylation in the colorectal adenoma‐carcinoma sequence and there was no significant association between promoter hyperethylation and other clinicopathologic characteristics of cancer.
Mapping of the methylation pattern of the hMSH2 promoter in colon cancer, using bisulfite genomic sequencing
This study mapped the complete methylation status of the hMSH2 promoter, a region that contains 75 CpG sites, using bisulfite genomic sequencing in 60 primary colorectal cancers and demonstrated that h MSH2 hypermethylation and protein expression were associated with the development of coloreCTal cancer.
Promoter methylation of P16, RARβ, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing
This data demonstrated p16 promoter methylation in a highly tumour specific pattern and Cytoglobin is a novel candidate tumour suppressor gene highly methylated in upper aero-digestive tract squamous cancer.
Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers
Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early tumor detection, and MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes.
CpG island methylation of genes accumulates during the adenoma progression step of the multistep pathogenesis of colorectal cancer
The aberrant methylation of genes appears to increase most significantly during the progression of early adenomas to advancedAdenomas, and the frequency of specific gene methylation at the different steps of the adenoma‐carcinoma progression sequence varies in a gene‐specific fashion.