title: PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population.
abstract: Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = <0.0001 and 0.017) for both PTEN and p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer.
authors.affiliation: Department of Pathology, National Institute of Nutrition (ICMR), Hyderabad, Telangana, India.
authors.forename: P S
authors.initials: PS
authors.lastname: Sushma
authors.affiliation: Department of Genetics, Bhagwan Mahavir Medical Research Centre, Hyderabad, 500004, Telangana, India. kj.bmmrc@gmail.com.
authors.forename: Kaiser
authors.initials: K
authors.lastname: Jamil
authors.affiliation: Department of Pathology, National Institute of Nutrition (ICMR), Hyderabad, Telangana, India.
authors.forename: P Uday
authors.initials: PU
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences, Chinnoutpalli, Gannavaram, A.P, India.
authors.forename: U
authors.initials: U
authors.lastname: Satyanarayana
authors.affiliation: MNJ Institute of Oncology and Regional Cancer Centre, Hyderabad, Telangana, India.
authors.forename: M
authors.initials: M
authors.lastname: Ramakrishna
authors.affiliation: MNJ Institute of Oncology and Regional Cancer Centre, Hyderabad, Telangana, India.
authors.forename: B
authors.initials: B
authors.lastname: Triveni
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis / Q000502:physiology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics*; D055088:Early Detection of Cancer; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Biomarkers; Epigenetics; Methylation-specific PCR (MSP); Oral squamous cell carcinoma (OSCC); PTEN; p16