title: ATM alterations in childhood non-Hodgkin lymphoma.
abstract: ATM gene alterations and impaired ATM protein expression have been described in various adult lymphoproliferative malignancies, suggesting that ATM contributes to lymphomagenesis. The present study investigated the prevalence of ATM gene and ATM protein expression alterations in sporadic childhood non-Hodgkin lymphoma (NHL). Twenty-seven cases of NHL were screened for ATM mutations by denaturing high-performance liquid chromatography (DHPLC). Direct and indirect criteria, including in silico tools, were used to classify the gene alterations. The methylation status of the ATM promoter CpG island was determined in 25 samples; ATM protein expression was assessed by Western blot in 9 lymphomas. ATM alterations were detected in 12 NHLs (44%). Ten different heterozygous base substitutions were identified in 10 NHLs (37%). Five samples (19%) were found to harbor a gene alteration considered to be a mutation or a rare variant potentially pathogenic. In one case, an ATM mutation was found in the germline. Four NHLs (44%) showed reduced or absent ATM protein expression. Except for one sample, no definite genetic or epigenetic alteration was identified to account for impaired ATM protein expression. These observations document a high prevalence of ATM gene and protein expression alterations, suggesting that ATM is involved in childhood NHL.
authors.affiliation: Department of Pediatrics, Unit of Hemato-Oncology, University Hospital of Geneva, Switzerland. Fabienne.GumyPause@medecine.unige.ch
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gumy-Pause
authors.forename: Pierre
authors.initials: P
authors.lastname: Wacker
authors.forename: Philippe
authors.initials: P
authors.lastname: Maillet
authors.forename: David R
authors.initials: DR
authors.lastname: Betts
authors.forename: André-Pascal
authors.initials: AP
authors.lastname: Sappino
mesh_terms: D000293:Adolescent; D064007:Ataxia Telangiectasia Mutated Proteins; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases