Aberrant methylation in pediatric myelodysplastic syndrome.
BACKGROUND
Aberrant methylation of gene promoter region is responsible for inappropriate gene silencing, and it has been associated to initiation and progression of cancer. Aberrant promoter methylation is frequently observed in adult patients with myelodysplastic syndrome (MDS), but in pediatric patients it has been poorly investigated.


METHODS
We examined the promoter methylation status of 13 genes in bone marrow cells collected at diagnosis of 21 pediatric patients with MDS (subtype RAEB or RAEB-t). For this analysis, we performed sodium bisulfite treatment of genomic DNA, followed by methylation specific PCR (MSP).


RESULTS
In pediatric MDS samples, we observed two genes frequently methylated: CALCA was methylated in 85.7% (18/21) of the analyzed samples and CDKN2B in 50% (6/12).


CONCLUSIONS
Our findings indicate that CALCA and CDKN2B are frequently methylated in pediatric MDS. It suggests that aberrant methylation in pediatric MDS seems to be similar to adult MDS, thus pediatric patients could be also benefited with treatment using demethylating agents.
Vidal
Daniel O
DO
Ludwig Institute for Cancer Research, São Paulo Branch, Rua Prof. Antônio Prudente, 109, 4 andar, CEP 01509-010 São Paulo, S.P., Brazil.
Paixão
Valéria A
VA
Brait
Mariana
M
Souto
Elisabeth X
EX
Caballero
Otávia L
OL
Lopes
Luiz Fernando
LF
Vettore
André L
AL
D000293:Adolescent; D002116:Calcitonin / Q000235:genetics*; D015740:Calcitonin Gene-Related Peptide; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D004247:DNA / Q000032:analysis; D019175:DNA Methylation; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011498:Protein Precursors / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods
C000606589:CALCA protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D011498:Protein Precursors; D002116:Calcitonin; D004247:DNA; D015740:Calcitonin Gene-Related Peptide