Epigenetic alterations of p15^INK4B and p16^INK4A genes in pediatric primary myelodysplastic syndrome

Abstract

We studied the methylation status of the p15^INK4B and p16^INK4A genes in 47 pediatric patients with primary MDS, its correlation with subtype, and the role of p15^INK4B and p16^INK4A in the evolution of MDS toward AML. Aberrant methylation of the p15^INK4B gene was detected in 15 of 47 patients (32%), whereas only four patients demonstrated methylation of the p16^INK4A gene (8%). The frequency of p15^INK4B methylation was significantly higher in RAEB and RAEB-t subtypes (p < 0.003). Aberrant methylation of the p16^INK4A gene was also more frequent in the subtypes that characterize advanced stages of the disease (p < 0.05). Evolution of disease was verified in 17 (36%) of the 47 patients. The association of p15^INK4B and p16^INK4A methylation status with evolution of disease was clearly significant (p < 0.008 and p < 0.05, respectively). These results suggest that methylation of the p15^INK4B and p16^INK4A genes is an epigenetic biomarker of pediatric disease evolution.

Keywords:

• p15^INK4B gene
• p16^INK4A gene
• pediatric myelodysplastic syndrome
• epigenetic
• methylation

Declaration of interest: This work was supported by Brazilian Ministry of Health (National Institute of Cancer/INCA, Brazil) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro/FAPERJ, Brazil (E-26/102.235/2009).