Epigenetic alterations of p15(INK4B) and p16(INK4A) genes in pediatric primary myelodysplastic syndrome.
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.
Rodrigues
Eliane F
EF
Bone Marrow Transplant Center, National Cancer Institute (INCA), Rio de Janeiro, Brazil.
Santos-Rebouças
Cíntia B
CB
Gonçalves Pimentel
Márcia M
MM
Mencalha
Andre L
AL
Dobbin
Jane
J
Da Costa
Elaine S
ES
Fernandez
Cecília de Souza
Cde S
Bouzas
Luis F
LF
Abdelhay
Eliana
E
De Souza Fernandez
Teresa
T
D000293:Adolescent; D000704:Analysis of Variance; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000235:genetics*; D016133:Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16