Inactivation of p16 by CpG hypermethylation in renal cell carcinoma.
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.
Vidaurreta
Marta
M
Department of Genomics Laboratory, Hospital Clínico San Carlos, Madrid, Spain.
Maestro
M Luisa
ML
Sanz-Casla
M Teresa
MT
Maestro
Carmen
C
Rafael
Sara
S
Veganzones
Silvia
S
Moreno
Jesus
J
Blanco
Julia
J
Silmi
Angel
A
Arroyo
Manuel
M
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
D019941:Cyclin-Dependent Kinase Inhibitor p16