Abstract
Purpose: The methylation status of the CpG promoter regions of the and genes, mutations of 4 exons of the CDKN2A gene, and the expression of the corresponding proteins were examined. Prognostic implications were assessed in osteosarcoma. Materials and Methods: Methylation-specific PCR, sequence analysis, and immunohistochemical staining were performed upon 32 frozen osteosarcoma tissues. Results: Methylation of was found in 16%, and methylation of in 47%. Metastasis and poor survival was statistically related to the methylation of . The methylation of correlated with the repression of the corresponding protein, and repression of with the repression of p21 and of wild type of p53. No sequence alterations were found in the four exons of the CDKN2A gene. Methylation of p14 showed highest hazard ratio by multivariate survival analysis. Conclusion: Our data suggest that methylation of the CDKN2A gene seems to be the main mechanism of protein repression. For , the methylation of its promoter region was related to the repression of p21 and wild type p53, distant metastasis and a poor prognosis. Further study regarding cell cycle regulatory factors should shed light on oncogenesis and the possibility of a new treatment strategy for osteosarcoma.
Published Version
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