title: TIMP3 and CCNA1 hypermethylation in HNSCC is associated with an increased incidence of second primary tumors.
abstract: BACKGROUND
  Hypermethylation in the promoter regions is associated with the suppression of gene expression and has been considered a potential molecular marker for several tumor types, including head and neck squamous cell carcinomas (HNSCC).
  
  
  METHODS
  To evaluate the gene hypermethylation profile as a prognostic marker, this retrospective study used a QMSP approach to determine the methylation status of 19 genes in 70 HNSCC patients.
  
  
  RESULTS
  The methylation profile analysis of primary HNSCC revealed that genes CCNA1, DAPK, MGMT, TIMP3 and SFRP1 were frequently hypermethylated, with high specificity and sensitivity. TIMP3 and CCNA1 hypermethylation was significantly associated with lower rates of second primary tumor-free survival (p = 0.007 and p = 0.001; log-rank test, respectively).
  
  
  CONCLUSIONS
  This study, for the first time, presents CCNA1 and TIMP3 hypermethylation as a helpful tool to identify HNSCC subjects at risk of developing second primary carcinomas.
authors.forename: Marianna Marconato
authors.initials: MM
authors.lastname: Rettori
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Carvalho
authors.forename: Ana Luiza Bomfim
authors.initials: AL
authors.lastname: Longo
authors.forename: Cleyton Zanardo
authors.initials: CZ
authors.lastname: de Oliveira
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Carvalho
authors.affiliation: Cancer Molecular Biology Laboratory, Department of Biological Sciences, Federal University of São Paulo, 04039-020, São Paulo, Brazil. andre.vettore@gmail.com.
authors.forename: André Luiz
authors.initials: AL
authors.lastname: Vettore
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D056750:Cyclin A1 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*
chemical_list: C503745:CCNA1 protein, human; D056750:Cyclin A1; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3