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.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p15/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA Methylation , Myelodysplastic Syndromes/genetics , Adolescent , Analysis of Variance , Base Sequence , Biomarkers, Tumor/genetics , Cell Line, Tumor , Child , Child, Preschool , Female , Humans , Infant , Male , Myelodysplastic Syndromes/classification , Polymerase Chain ReactionABSTRACT
Um estudo foi realizado com 20 pacientes com distrofia muscular Duchenne (DMD) e 4 com distrofia muscular Becker (BMD), com o objetivo de expor deleçöes e duplicaçöes na extremidade 5' do gene da distrofina com a sonda XJ10 (1-2b) e na regiäo central do gene com as sondas cDNA 7b-8 e 44-1 (8). Todas as 7 deleçöes e 1 duplicaçäo DMD da regiäo central do gene foram detectadas com a sonda 44-1 (8), enquanto as 2 deleçöes DMB foram melhor detectadas com a sonda 7b-8. A sonda genômica P20 serviu para delimitar proximalmente a extensäo destas deleçöes. A sonda XJ10 (1-2b) detectou 1 deleçäo e 1 duplicaçäo DMD. Deste modo, foram detectadas, por Southern, 12 alteraçöes genômicas num total de 24 pacientes (50%). Neste estudo o subsídio da PCR foi importante para confirmar a presença ou ausência de fragmentos de baixo peso molecular que se perderam em algumas corridas. Ficou confirmado que a sonda 8 (44-1) é ideal para detectar deleçöes DMD e a 7b-8 para detectar deleçöes DMD e DMB, já que a maioria das deleçöes DMB comprometem os exons 45 e 46, com ponto de quebra em P20, uma regiäo contida num imenso intron (44-45), de 170 kb. Um possível hotspot (XJ) foi observado nas duas unicas alteraçöes genômicas detectadas com a sonda XJ10 (intron 7-8)
