Promoter hypermethylation and expression profile of MGMT and CDH1 genes in oral cavity cancer.
BACKGROUND
Several genetic alterations have been reported to contribute to the development of oral squamous cell carcinoma (OSCC). Methylation of CpG-islands in cancer-related genes may serve as epigenetic biomarkers for oral cancer diagnosis and prognosis. The objective of this study was to analyze methylation profile of MGMT and CDH1 genes and their link with expression activity in patients with oral cavity cancer.


METHODS
Promoter hypermethylation status of MGMT and CDH1 genes were assayed by Methylation-specific PCR (MSP) in OSCC (n=76) tissues kept in paraffin and normal oral tissues (n=57) served as control. Also, we investigated MGMT and CDH1 mRNA levels by real-time quantities reverse transcripts PCR. Methylation and mRNA expression profiles of these genes and their association with clinical data were determined.


RESULTS
Aberrant promoter hypermethylation of CDH1 and MGMT genes were detected in 61.8% (47 of 76) and 73.7% (56 of 76) of the OSCC cases, respectively, with significant difference between cases and controls for MGMT (P=0.027). CDH1 promoter methylation in cases and healthy controls was not significant. The mRNA expression level results showed statistically significant (P=0.03) differences between cases and healty controls for the MGMT gene. However, the difference for the CDH1 gene was not significant.


CONCLUSIONS
Our findings, for the first time, in a South-Eastern Iranian population, indicate that the two genes are aberrantly methylated in OSCC, and that MGMT methylation may be considered as a potential molecular marker for the poor survival in advanced OSCC.
Kordi-Tamandani
Dor Mohammad
DM
Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran. dor_kordi@science.usb.ac.ir
Moazeni-Roodi
Abdul-Karim
AK
Rigi-Ladiz
Mohammad-Ayub
MA
Hashemi
Mohammad
M
Birjandian
Elnaz
E
Torkamanzehi
Adam
A
D000328:Adult; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes