title: Inactivation of p16 by CpG hypermethylation in renal cell carcinoma.
abstract: OBJECTIVE
  Renal carcinoma develops as a consequence of the accumulation of several genetic aberrations. Alterations in the p16 gene have been described in many tumors. Methylation of its promoter in CpG islands is the most common mechanism of inactivation of this gene. The aim of this study was to establish whether p16 gene methylation leads to a loss of the encoded protein in 57 patients with renal carcinoma, and if this aberration has any value in predicting disease progression in these patients.
  
  
  METHODS
  Gene promoter methylation was determined by deoxyribonucleic acid treated with sodium bisulfite to subsequently amplify methylated and unmethylated regions rich in CpG islands. The p16 protein product was detected for immunohistochemical examination.
  
  
  RESULTS
  Hypermethylation of the p16 gene was detected in 22.9% of the patients, none of whom had the protein product. A lack of p16 protein was confirmed in 52.9% of the tumors, indicating another genetic alteration or posttranscriptional modifications preventing the codification of this protein. Through multivariate analysis of overall survival, gene methylation was found to have independent prognostic value: the absence of alteration confers an undefined risk of death.
  
  
  CONCLUSIONS
  Of the molecular modifications described for renal carcinoma, aberrations in the p16 gene are frequent. In these patients, methylation of the p16 gene promoter seems to afford a protective effect against the risk of death.
authors.affiliation: Department of Genomics Laboratory, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Vidaurreta
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Maestro
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Sanz-Casla
authors.forename: Carmen
authors.initials: C
authors.lastname: Maestro
authors.forename: Sara
authors.initials: S
authors.lastname: Rafael
authors.forename: Silvia
authors.initials: S
authors.lastname: Veganzones
authors.forename: Jesus
authors.initials: J
authors.lastname: Moreno
authors.forename: Julia
authors.initials: J
authors.lastname: Blanco
authors.forename: Angel
authors.initials: A
authors.lastname: Silmi
authors.forename: Manuel
authors.initials: M
authors.lastname: Arroyo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018899:CpG Islands / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16