title: TP53 is frequently altered by methylation, mutation, and/or deletion in acute lymphoblastic leukaemia.
abstract: Different mechanisms, such as chromosomal rearrangements, deletions, mutations, and methylation/demethylation of the promoter regions of genes, have been shown to be involved in acute lymphoblastic leukaemia (ALL). These genetic and epigenetic alterations lead to the activation of protooncogenes or to inactivation of tumour suppressor genes promoting cell proliferation. One of the most frequently inactivated tumour suppressor genes is TP53, which is altered in 50% of human tumours. In this study, we have analysed: (1) the complete coding region, all intron-exon junctions and noncoding regions of exons 1-11 of TP53 by lexon-DGGE; (2) the methylation status of the 5' region of TP53 and (3) the deletion of one or both alleles of the gene by fluorescence in situ hybridisation (FISH) in 57 ALL patients. Using these techniques, we have found promoter methylation in 32% of the cases, missense mutations in 8.8%, and deletion of one allele in 7.5% of the samples, with TP53 being altered in 40% of the ALL samples studied in this series.
authors.affiliation: Department of Genetics, School of Sciences, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Agirre
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Novo
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: María J
authors.initials: MJ
authors.lastname: Larráyoz
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Mikel
authors.initials: M
authors.lastname: Valgañón
authors.forename: Marina
authors.initials: M
authors.lastname: García-Delgado
authors.forename: José L
authors.initials: JL
authors.lastname: Vizmanos
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D017353:Gene Deletion; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D020868:Gene Silencing; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm