RGD Reference Report - Aberrant methylation of different DNA repair genes demonstrates distinct prognostic value for esophageal cancer. - Rat Genome Database

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Aberrant methylation of different DNA repair genes demonstrates distinct prognostic value for esophageal cancer.

Authors: Ling, Zhi-Qiang  Li, Pei  Ge, Ming-Hua  Hu, Fu-Jun  Fang, Xian-Hua  Dong, Zi-Min  Mao, Wei-Min 
Citation: Ling ZQ, etal., Dig Dis Sci. 2011 Oct;56(10):2992-3004. doi: 10.1007/s10620-011-1774-z. Epub 2011 Jun 15.
RGD ID: 126790574
Pubmed: (View Article at PubMed) PMID:21674174
DOI: Full-text: DOI:10.1007/s10620-011-1774-z


BACKGROUND: DNA mismatch repair (MMR) deficiency results in a strong mutator phenotype and high-frequency microsatellite instability (MSI-H), which are the hallmarks of many tumors.
AIM: The objective of this study is to investigate the promoter CpG island methylation status of mismatch repair genes human mutL homolog 1 (hMLH1), human mutS homolog 2 (hMSH2), and O(6)-methylguanine-DNA methyltransferase (MGMT) in esophageal squamous cell carcinoma (ESCC) and its roles in alkylating agents chemotherapy.
METHODS: Real-time methylation-specific polymerase chain reaction (PCR) (real-time MSP) was employed to detect promoter CpG island methylation of the hMLH1, hMSH2, as well as MGMT genes in 235 surgical tumor tissue samples from ESCC patients and their corresponding normal tissue samples.
RESULTS: Promoter CpG island methylation of hMLH1, hMSH2, and MGMT were detectable in 43.4, 28.9, and 40.4% of ESCC tumor DNA, respectively, and the loss rates of hMLH1, hMSH2, and MGMT protein expression were 48.6, 34.5, and 40.9% in tumor tissues, respectively. For the entire population of 235 ESCC patients who were enrolled in operating treatment combined with radiotherapy and chemotherapy with alkylating agents, there was a significant difference in the overall survival between patients with methylated MGMT promoter and those with an unmethylated MGMT promoter (P < 0.05).
CONCLUSION: Promoter CpG island methylation may be a frequent event in ESCC carcinogenesis. Detection of the methylated sequences of hMLH1, hMSH2, and MGMT appears to be promising as a predictive factor in primary ESCC.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Mgmt  (O-6-methylguanine-DNA methyltransferase)
Mlh1  (mutL homolog 1)
Msh2  (mutS homolog 2)

Genes (Mus musculus)
Mgmt  (O-6-methylguanine-DNA methyltransferase)
Mlh1  (mutL homolog 1)
Msh2  (mutS homolog 2)

Genes (Homo sapiens)
MGMT  (O-6-methylguanine-DNA methyltransferase)
MLH1  (mutL homolog 1)
MSH2  (mutS homolog 2)


Additional Information