title: Expression and promoter methylation status of hMLH1, MGMT, APC, and CDH1 genes in patients with colon adenocarcinoma.
abstract: Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. CRC development is the result of genetic and epigenetic alterations accumulation in the epithelial cells of colon mucosa. In the present study, DNA methylation, an epigenetic event, was evaluated in tumoral and matching normal epithelium in a cohort of 61 CRC patients. The results confirmed and expanded knowledge for the tumor suppressor genes hMLH1, MGMT, APC, and CDH1. Promoter methylation was observed for all the examined genes in different percentage. A total of 71% and 10% of the examined cases were found to be methylated in two or more and in all genes, respectively. mRNA and protein levels were also evaluated. Promoter methylation of hMLH1, MGMT, APC, and CDH1 genes was present at the early stages of tumor's formation and it could also be detected in the normal mucosa. Correlations of the methylated genes with patient's age and tumor's clinicopathological characteristics were also observed. Our 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.
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Michailidi
authors.affiliation: First Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
authors.affiliation: Second Department of Propedeutic Surgery, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Tsourouflis
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, Division of Biological Research & Biotechnology, National Hellenic Research Foundation, Athens 11635, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Pletsa
authors.affiliation: Second Department of Propedeutic Surgery, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Gregorios
authors.initials: G
authors.lastname: Kouraklis
authors.affiliation: First Department of Pathology, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens 11527, Greece ktrougkos@med.uoa.gr papavas@med.uoa.gr.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Troungos
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C555337:APC protein, human; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes
keywords: Colon cancer; CpG islands; epigenetics; methylation; methylation-specific PCR