Aberrant methylation in promoter-associated CpG islands of multiple genes in relapsed childhood acute lymphoblastic leukemia.
Methylation profile was analyzed in nine cases of relapsed childhood acute lymphoblastic leukemia (ALL) for p14, p15, p16, Rb, MGMT, APC, hMLH1, RARbeta, RIZ, DAPK, and FHIT genes by using methylation specific polymerase chain reaction (MSP) analysis. Frequency of methylation in each gene was: MGMT, 56%; RARbeta, 44%; and p16, 22%, respectively. None of the p14, p15, Rb, APC, hMLH1, RIZ, DAPK, and FHIT genes were hypermethylated. Five (56%) of 9 cases showed methylation of at least one gene. All of the samples with hypermethylation in p16 and MGMT gene at relapse, had already acquired the change at the time of initial diagnosis. Interestingly, three of 4 cases with RARbeta gene methylation at relapse did not have methylation of this gene at the time of initial presentation. These results suggest that hypermethylation might be involved in the relapse of childhood ALL.
Matsushita
Chise
C
Department of Medicine, Kochi Medical School, Kochi 783-8505, Japan.
Yang
Yang
Y
Takeuchi
Seisho
S
Matsushita
Masahide
M
Van Dongen
Jacques J M
JJ
Szczepanski
Tomasz
T
Bartram
Claus R
CR
Seo
Hiromi
H
Koeffler
H Phillip
HP
Taguchi
Hirokuni
H
D000293:Adolescent; D001854:Bone Marrow Cells / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D017491:Genes, APC; D016161:Genes, Retinoblastoma; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*
D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide