Aberrant methylation of p14ARF gene correlates with poor survival in osteosarcoma.
We studied the methylation status of the CpG promoter regions of the p16 and p14 genes, mutations of four exons of the CDKN2A gene, and expressions of their corresponding proteins. Thirty-two frozen osteosarcoma tissues were used for methylation-specific polymerase chain reaction and sequence analysis. Immunohistochemical staining for p16 and p14 proteins was done. The histologic and clinical data were analyzed to find their prognostic implications. The promoter of p16 gene was methylated in 16%, and p14 in 47%. Poor survival was related to methylation of p14. The methylation of p14 correlated with down-regulation of its protein expression. The methylation of p14 showed the highest hazard ratio by multivariate survival analysis. Our data suggest methylation of the CDKN2A gene is the main mechanism of its protein repression. For the p14 gene, methylation of the promoter region was related to repression of p14 protein and poor prognosis.


METHODS
Prognostic study, Level II (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.
Oh
Joo Han
JH
Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul, Korea.
Kim
Han-Soo
HS
Kim
Hyung-Ho
HH
Kim
Woo Ho
WH
Lee
Sang Hoon
SH
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005091:Exons; D005260:Female; D015870:Gene Expression; D019942:Genes, p16; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D016019:Survival Analysis; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D025803:Tumor Suppressor Protein p14ARF