title: Association of ataxia telangiectasia mutated (ATM) gene mutation/deletion with rhabdomyosarcoma.
abstract: Rhabdomyosarcoma is a common malignancy in children. There are two major types of rhabdomyosarcomas, the embryonal and the alveolar, differing in cytogenetic and morphologic features. The alveolar type of rhabdomyosarcoma is frequently associated with chromosome translocation t(2; 13) and poor clinical prognosis. Pathogenesis of rhabdomyosarcoma remains obscure, and especially it occurs in the location where skeletal muscle is absent. We report here that there is a high frequency of association of rhabdomyosarcoma with ataxia telangiectasia mutated (ATM) gene mutation/deletion. Totally 17 cases of rhabdomyosarcoma specimens were studied by immunohistochemical or immunofluorescent staining with ATM antibody and revealed that 7 of the 17 cases were negative for ATM expression (41%). Further analyses of rhabdomyosarcoma cell lines with RT-PCR revealed that in Rh30 cells, an alveolar rhabdomyosarcoma cell line, there are three separate deletions/mutations of the ATM mRNA. Western blotting analysis of the Rh30 cellular extract with anti-ATM antibody showed that there is an aberrant form of ATM protein within the Rh30 cells that are smaller than normal control. These results suggest, for the first time, a link of ATM gene deletion/mutation with rhabdomyosarcoma, and since ATM kinase is a crucial regulatory protein in DMA damage repair signaling pathway, and ATM deletion/mutation may contribute to pathogenesis of rhabdomyosarcoma.
authors.affiliation: Department of Pathology, West Virginia University Health Sciences Center, Morgontown, West Virginia 26506-9203, USA. pzhang@hsc.wvu.edu
authors.forename: Peilin
authors.initials: P
authors.lastname: Zhang
authors.forename: Kunjan S
authors.initials: KS
authors.lastname: Bhakta
authors.forename: Pier Lorenzo
authors.initials: PL
authors.lastname: Puri
authors.forename: Robert O
authors.initials: RO
authors.lastname: Newbury
authors.forename: James R
authors.initials: JR
authors.lastname: Feramisco
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D002882:Chromosomes, Human, Pair 13; D002889:Chromosomes, Human, Pair 2; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D005091:Exons; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012208:Rhabdomyosarcoma / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured / Q000473:pathology; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases