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Updated: Jul 5, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Inactivation of p16 by CpG hypermethylation in renal cell carcinoma
Marta Vidaurreta1, M Luisa Maestro, M Teresa Sanz-Casla
1Department of Genomics Laboratory, Hospital Clínico San Carlos, Madrid, Spain.
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.
Insights
p16 gene promoter methylation in renal carcinoma patients was linked to a lack of p16 protein. This methylation appears to protect against death, suggesting a potential prognostic marker for kidney cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal carcinoma arises from accumulated genetic aberrations.
- p16 gene alterations are common in various tumors.
- Promoter methylation is a frequent mechanism for p16 gene inactivation.
Purpose of the Study:
- To determine if p16 gene methylation causes protein loss in renal carcinoma.
- To assess the prognostic value of p16 gene methylation in predicting disease progression.
Main Methods:
- DNA methylation analysis using bisulfite treatment and PCR.
- Immunohistochemistry to detect p16 protein expression.
Main Results:
- p16 gene promoter hypermethylation found in 22.9% of patients, with no detectable protein.
- Absence of p16 protein in 52.9% of tumors, suggesting other inactivation mechanisms.
- Multivariate analysis revealed p16 gene methylation as an independent prognostic factor for survival.
Conclusions:
- p16 gene aberrations are frequent in renal carcinoma.
- p16 gene promoter methylation may confer a protective effect against mortality in these patients.
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