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KMID : 0361620030380060631
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Journal of the Korean Orthopaedic Association
2003 Volume.38 No. 6 p.631 ~ p.640
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Significance of the Methylation of Cyclin-Dependent Kinase Inhibitor 2A gene in the Prognosis of Osteosarcoma
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Abstract
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Purpose : The metflylation status. of the CpG promoter regions of the p16´x`" ancf p14"´~ genes, mutations of 4 axons of the CDKN2A gene, and the expression of the corresponding proteins were examined. Prognostic implications were assessed in osteosarcoma.
AAaterials and Methods : Methylation-specific PCR, sequence analysis, and immunohistochemical staining were performed upon 32 frozen osteosarcorrla tissues.
Results : Methylation of p16N`"´` was found in 16%, and memylamon of p14"´~ in 47%. Metastasis and poor survival was statistically related to the methylation of p14^´~. The methylation of p14`´~ correlated wish the repression of the corresponding protein. and represses of p14´"~ with the repression of p21 and of wild type of p53. No sequence alterations were found in the four axons 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 mectlanism of protein repression. For p14"´~, 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 orx;ogenesis and the possibility of a new treatment strategy for osteosarcoma.
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