title: Hypermethylation of RUNX3 but not WIF1 gene and its association with stage and nodal status of tongue cancers.
abstract: OBJECTIVE
  Recent studies indicate various molecular abnormalities in oral squamous cell carcinomas (OSCC), including DNA methylation of tumor-associated genes. Although promoter hypermethylation of Wnt pathway antagonists RUNX3 (Runt-related transcription factor 3) and Wnt inhibitory factor 1 (WIF1) has been identified as a common event in a number of carcinomas, methylation status and the role of RUNX3 as a possible tumor suppressor in oral and head and neck cancer are yet controversial. The aim of our study is to determine the occurrence of RUNX3 and WIF1 genes hypermethylation and correlation with tumor and host-related factors and prognosis in tongue carcinomas.
  
  
  METHODS
  In 76 patients with tongue carcinoma, RUNX3 and WIF1 genes promoter hypermethylation analysis was assessed by nested methylation-specific PCR method.
  
  
  RESULTS
  Hypermethylation of WIF1 and RUNX3 genes promoters was observed in 35% and 25% of carcinomas, respectively. RUNX3 gene promoter hypermethylation was significantly associated with lymph node involvement (P = 0.013) and tumor stage (P = 0.006), but not with the overall survival. Occurrence of RUNX3 and WIF1 genes comethylation was associated with nodal status (P = 0.058) and tumor stage (P = 0.055).
  
  
  CONCLUSIONS
  Our findings indicate that RUNX3 and WIF1 are frequently aberrantly methylated and that RUNX3 promoter methylation could be considered as a potential prognostic marker in tongue carcinoma.
authors.affiliation: Institute for Medical Research, Military Medical Academy, Belgrade, Serbia. gogasupic@sezampro.rs
authors.forename: G
authors.initials: G
authors.lastname: Supic
authors.forename: R
authors.initials: R
authors.lastname: Kozomara
authors.forename: N
authors.initials: N
authors.lastname: Jovic
authors.forename: K
authors.initials: K
authors.lastname: Zeljic
authors.forename: Z
authors.initials: Z
authors.lastname: Magic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D015331:Cohort Studies; D050677:Core Binding Factor Alpha 3 Subunit / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*; D012907:Smoking; D015996:Survival Rate; D014062:Tongue Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; D012097:Repressor Proteins; C493729:Runx3 protein, human; C485569:WIF1 protein, human