Quantitative comparison of CDKN2B methylation in pediatric and adult myelodysplastic syndromes.

ABSTRACT

BACKGROUND/AIMS: Transcriptional repression of tumor suppressor genes is determined by the quantity of promoter hypermethylation. We analyzed the methylation quantity of CDKN2B in pediatric myelodysplastic syndromes (MDS). METHODS: Quantitative measurement of CDKN2B methylation was performed in 25 pediatric MDS patients and 12 controls using pyrosequencing, and the result was compared with those from 74 adult MDS cases and 31 adult controls. The association between CDKN2B methylation quantity and factors related to prognosis including bone marrow blast percentage and karyotype was analyzed. RESULTS: Pediatric MDS patients showed a higher methylation level (MtL) of CDKN2B than pediatric controls (2.94 vs. 1.62; p = 0.031) but a lower level than adult MDS patients (8.76; p < 0.001). MtL was higher in pediatric MDS cases with >5% blasts than in pediatric controls (3.78 vs. 1.62; p = 0.052). Pediatric MDS cases with abnormal karyotype showed a higher MtL than pediatric controls (5.95 vs. 1.62; p = 0.045). CONCLUSIONS: We confirmed that methylation of CDKN2B is associated with the pathogenesis and prognosis in pediatric MDS. The difference in MtLs between pediatric and adult MDS might be related to the physiological hypermethylation of tumor suppressor genes in aging.