Methylation of CpG dinucleotides and/or CCWGG motifs at the promoter of TP53 correlates with decreased gene expression in a subset of acute lymphoblastic leukemia patients.
It has been shown that methylation of CpG dinucleotides located in the promoter region of TP53 is associated with low expression levels of this gene. We have analysed the methylation status of one CpG dinucleotide and of three CCWGG motifs, also located in the promoter region of the gene, in bone marrow samples obtained from patients with acute lymphoblastic leukemia (ALL). Eight out of 25 samples analysed showed methylation of either the CpG dinucleotide, the CCWGG motifs or both. Relative to nonmethylated leukemia samples, TP53 expression levels were decreased in all methylated samples in which TP53 expression could be measured. Methylation of CpG and CCWGG motifs in the promoter of TP53 could represent a novel mechanism leading to functional impairment of this tumor suppressor gene in ALL.
Agirre
Xabier
X
Department of Genetics, School of Sciences, University of Navarra, E-31080 Pamplona, Navarra, Spain.
Vizmanos
José Luis
JL
Calasanz
María J
MJ
García-Delgado
Marina
M
Larráyoz
María J
MJ
Novo
Francisco J
FJ
D001853:Bone Marrow / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D020868:Gene Silencing; D016158:Genes, p53; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D037941:Silencer Elements, Transcriptional; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53