title: Promoter region hypermethylation and mRNA expression of MGMT and p16 genes in tissue and blood samples of human premalignant oral lesions and oral squamous cell carcinoma.
abstract: Promoter methylation and relative gene expression of O(6)-methyguanine-DNA-methyltransferase (MGMT) and p16 genes were examined in tissue and blood samples of patients with premalignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC). Methylation-specific PCR and reverse transcriptase PCR were performed in 146 tissue and blood samples from controls and patients with PMOLs and OSCC. In PMOL group, significant promoter methylation of MGMT and p16 genes was observed in 59% (P = 0.0010) and 57% (P = 0.0016) of tissue samples, respectively, and 39% (P = 0.0135) and 33% (P = 0.0074) of blood samples, respectively. Promoter methylation of both genes was more frequent in patients with OSCC, that is, 76% (P = 0.0001) and 82% (P = 0.0001) in tissue and 57% (P = 0.0002) and 70% (P = 0.0001) in blood, respectively. Significant downregulation of MGMT and p16 mRNA expression was observed in both tissue and blood samples from patients with PMOLs and OSCC. Hypermethylation-induced transcriptional silencing of MGMT and p16 genes in both precancer and cancer suggests important role of these changes in progression of premalignant state to malignancy. Results support use of blood as potential surrogate to tissue samples for screening or diagnosing PMOLs and early OSCC.
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow 226003, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Bhatia
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow 226003, India.
authors.forename: Madhu Mati
authors.identifier: 0000-0001-7033-184X
authors.initials: MM
authors.lastname: Goel
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow 226003, India.
authors.forename: Annu
authors.initials: A
authors.lastname: Makker
authors.affiliation: Petroleum Toxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226003, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Tewari
authors.affiliation: Department of Biochemistry, Saraswati Dental College, Lucknow 227105, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Yadu
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow 226003, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shilpi
authors.affiliation: All India Institute of Medical Sciences, Bhopal, Madhya Pradesh 462026, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Otorhinolaryngology, King George's Medical University, Lucknow 226003, India.
authors.forename: S P
authors.initials: SP
authors.lastname: Agarwal
authors.affiliation: Petroleum Toxicology Division, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow 226003, India ; Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh 462026, India.
authors.forename: Sudhir K
authors.initials: SK
authors.lastname: Goel
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes