title: ATM gene mutations are not involved in medulloblastoma in children.
abstract: Primitive neuroectodermal tumors (PNET)-medulloblastomas account for approximately 20% of all brain tumors in children. Ataxia-telangiectasia is an autosomal recessive neurological disorder with predisposition to cancer. The most common neoplasms are lymphoid malignancies and solid tumors, including central nervous system tumors, astrocytomas, and medulloblastomas. To investigate the potential role of the ATM gene in the pathogenesis of medulloblastoma, 13 tumors were screened for ATM mutations and 9 for loss of heterozygosity (LOH) of the ATM locus and flanking regions. In none of the tumors were mutations identified. In five of them, the well-known polymorphisms D1853N and F858L were identified and in all 22 tumors, the wild-type allele was preserved. The frequency of the polymorphisms was similar to that reported in our and other normal populations. The LOH of the 11q region (including the ATM gene), detected in 25% of informative cases, is consistent with the molecular and cytogenetic reports of deletion of chromosome 11 in 13%-41% of medulloblastomas. These results indicate that mutations in the ATM gene do not play a role in the pathogenesis of medulloblastoma in children. The LOH in the 11q region may suggest hidden unidentified tumor suppressor genes that may be involved in the malignant transformation.
authors.affiliation: Molecular Oncology, Felsenstein Medical Research Center, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Liberzon
authors.forename: Smadar
authors.initials: S
authors.lastname: Avigad
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Cohen
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Shalom
authors.initials: S
authors.lastname: Michovitz
authors.forename: Rina
authors.initials: R
authors.lastname: Zaizov
mesh_terms: D000293:Adolescent; D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D004268:DNA-Binding Proteins; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008527:Medulloblastoma / Q000235:genetics*; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D025521:Tumor Suppressor Proteins
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