title: Methylation of the APAF-1 and DAPK-1 promoter region correlates with progression of renal cell carcinoma in North Indian population.
abstract: Aberrant promoter hypermethylation of cancer associated genes occur frequently during carcinogenesis and may serve as a cancer biomarker. The aim of this study was to investigate the occurrence and relevance of promoter methylation of the tumor suppressor DAPK-1, APAF-1 () and SPARC in relation to different pathological stages and histological grades of tumor progression that might act as possible independent prognostic factor in the susceptibility towards renal cell carcinoma (RCC) in North Indian population. Three tumor suppressor gene promoters namely APAF-1, DAPK-1 and SPARC were assessed by methylation-specific PCR (MS-PCR) in 196 primarily resected renal cell tumors paired with the corresponding normal tissue samples. After genomic DNA isolation and sodium bisulfite modification, methylation levels were determined and correlated with standard clinicopathological parameters, pathological stage and Fuhrman nuclear grade of RCC. Significant differences in methylation frequency among the four subtypes of renal tumors were found for APAF-1 (p < 0.001), DAPK-1 (p < 0.001) and SPARC (p = 0.182), when compared with the corresponding normal tissue. Male subjects showed stronger association of methylation frequency of all the three genes with RCC than the female subjects. Additionally, higher frequency of APAF-1, DAPK-1 and SPARC promoter methylation were directly correlated with higher tumor stage (p (trend) < 0.001). Higher frequency of promoter methylation of APAF-1 and SPARC were also associated with higher nuclear grade (p < 0.001 and p = 0.036, respectively). This gene panel might contribute to a more optimal diagnostic coverage and information, improving preoperative assessment and therapeutic decision-making in patients harboring suspicious renal masses.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, Hamdard University, Hamdard Nagar, New Delhi, 110062, India.
authors.forename: Shiekh Tanveer
authors.initials: ST
authors.lastname: Ahmad
authors.forename: Wani
authors.initials: W
authors.lastname: Arjumand
authors.forename: Amlesh
authors.initials: A
authors.lastname: Seth
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Saini
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D018450:Disease Progression; D005260:Female; D006801:Humans; D007194:India; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D015676:Osteonectin / Q000235:genetics; D011401:Promoter Regions, Genetic
chemical_list: C506592:APAF1 protein, human; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; D015676:Osteonectin; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases