Promoter methylation status of MGMT, hMSH2, and hMLH1 and its relationship to corresponding protein expression and TP53 mutations in human esophageal squamous cell carcinoma

Yaoyao Su; Lihong Yin; Ran Liu; Jingyi Sheng; Miao Yang; Yi Wang; Enchun Pan; Wei Guo; Yuepu Pu; Juan Zhang; Geyu Liang

doi:10.1007/s12032-013-0784-4

Promoter methylation status of MGMT, hMSH2, and hMLH1 and its relationship to corresponding protein expression and TP53 mutations in human esophageal squamous cell carcinoma

Med Oncol. 2014 Feb;31(2):784. doi: 10.1007/s12032-013-0784-4. Epub 2013 Dec 24.

Authors

Yaoyao Su¹, Lihong Yin, Ran Liu, Jingyi Sheng, Miao Yang, Yi Wang, Enchun Pan, Wei Guo, Yuepu Pu, Juan Zhang, Geyu Liang

Affiliation

¹ Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.

PMID: 24366688
DOI: 10.1007/s12032-013-0784-4

Abstract

To determine the relevance of O-6-methylguanine-DNA methyltransferase (MGMT), human mutS homolog 2 (hMSH2), and human mutL homolog 1 (hMLH1) in TP53 mutations in esophageal squamous cell carcinoma, we employed methylation-sensitive high-resolution melting technology and methylation-specific polymerase chain reaction (PCR) to analyze promoter hypermethylation of MGMT, hMSH2, and hMLH1, respectively, in 51 paired tumors and their adjacent normal tissues. The protein expression of the three proteins was also evaluated by Western blot analysis, and the PCR products of TP53, from exon 5 to exon 8, were directly sequenced to measure the mutation spectrum. Esophageal tumor tissues embraced statistically higher MGMT and hMSH2 promoter methylation level than normal tissue. The promoter methylation status of MGMT and hMSH2 corresponds positively with the protein expression level of MGMT and hMSH2. However, such relevance was not found for hMLH1. Furthermore, TP53 mutation status was well associated with MGMT and hMSH2 promoter methylation status, indicating that silencing of the two genes could lead to TP53 mutation in ESCC.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Blotting, Western
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
DNA Methylation*
DNA Modification Methylases / genetics*
DNA Modification Methylases / metabolism
DNA Repair / genetics
DNA Repair Enzymes / genetics*
DNA Repair Enzymes / metabolism
DNA, Neoplasm / genetics
Esophageal Neoplasms / genetics*
Esophageal Neoplasms / metabolism
Esophageal Neoplasms / pathology
Esophagus / metabolism
Esophagus / pathology
Humans
Microsatellite Repeats
MutL Protein Homolog 1
MutS Homolog 2 Protein / genetics*
MutS Homolog 2 Protein / metabolism
Mutation / genetics*
Neoplasm Grading
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Polymerase Chain Reaction
Prognosis
Promoter Regions, Genetic / genetics*
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
Tumor Suppressor Proteins / genetics*
Tumor Suppressor Proteins / metabolism

Substances

Adaptor Proteins, Signal Transducing
DNA, Neoplasm
MLH1 protein, human
Nuclear Proteins
TP53 protein, human
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
DNA Modification Methylases
MGMT protein, human
MSH2 protein, human
MutL Protein Homolog 1
MutS Homolog 2 Protein
DNA Repair Enzymes