title: Molecular variants of the ATM gene in Hodgkin's disease in children.
abstract: Ataxia telangiectasia is an autosomal recessive disease with a striking predisposition of lymphoid malignancies. ATM mutations have been reported in adult sporadic lymphoma and leukaemia. The aim of this study was to investigate the possible involvement of the ATM gene in the carcinogenesis of Hodgkin disease in children. Tumours were obtained from 23 patients and were subjected to mutation screening and loss of heterozygosity analysis. Eight base substitutions were identified in seven patients. Of them, Y54Y, a silent change, was observed in two patients and a known polymorphism, D1853N, in three patients. Of the other two patients, one harboured a combined genotype P604S/F1463C, identified previously in two patients with Hodgkin lymphoma, and the other a novel missense mutation, V595A. The alterations were present in the germ line, and both had a more aggressive disease. In all, 100 matched normal ethnic controls were screened for these mutations and P604S/F1463C was identified in one healthy control. Loss of heterozygosity was identified in four patients and in three of them it was located centromeric to the ATM gene, and, in one, it spanned a large region, indicating the involvement of other tumour-suppressor genes in this disease. Missense variants of the ATM gene are a rare event in childhood Hodgkin disease.
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Petah Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Liberzon
authors.forename: S
authors.initials: S
authors.lastname: Avigad
authors.forename: I
authors.initials: I
authors.lastname: Yaniv
authors.forename: B
authors.initials: B
authors.lastname: Stark
authors.forename: G
authors.initials: G
authors.lastname: Avrahami
authors.forename: Y
authors.initials: Y
authors.lastname: Goshen
authors.forename: R
authors.initials: R
authors.lastname: Zaizov
mesh_terms: D000293:Adolescent; D001260:Ataxia Telangiectasia; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006689:Hodgkin Disease / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D016350:Leucine Zippers; D019656:Loss of Heterozygosity; D008297:Male; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human