title: ATM gene alterations in childhood acute lymphoblastic leukemias.
abstract: Hereditary ATM gene mutations cause ataxia-telangiectasia, a pleiotropic disorder associated with a high incidence of lymphoid malignancies. Acquired ATM alterations have been described in sporadic lymphoproliferative disorder suggesting that the ATM gene contributes to lymphomagenesis. To assess the prevalence of genomic ATM alterations in childhood acute lymphoblastic leukemias (ALL), we explored a series of 57 sporadic ALL cases (26 B-precursor ALL and 31 T-ALL) using DHPLC (Denaturing High-Performance Liquid Chromatography). We identified 28 distinct genomic ATM alterations in 14 patients (25%). Ten of them were scored as probably biologically significant and appear to be associated with a high risk of relapse (P<0.01). Six alterations of potential biological significance were observed in 5 cases of B-precursor ALL (19%), while 5 were found in 3 cases of T-ALL (10%). In two cases of B-precursor ALL, the ATM alterations were found in the germline, indicating an ATM carrier status. We report here the high prevalence of genomic ATM alterations in childhood ALL. Our observations lend further support to the postulated contribution of ATM in lymphomagenesis.
authors.affiliation: Department of Pediatrics, Unit of Hematology/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
authors.initials: D
authors.lastname: Betts
authors.forename: André-Pascal
authors.initials: AP
authors.lastname: Sappino
mesh_terms: D000293:Adolescent; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases