title: Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient.
abstract: We observed severe late effects in a patient treated with radiation therapy for breast cancer. Radiation survival studies of patient fibroblasts show an enhanced cellular radiation sensitivity (Do = 0.95 Gy). Genetic analysis reveals that the patient is heterozygous for a mutated ATM gene. Protein truncation test (PTT) and sequence analysis identified a truncation within the leucine zipper domain, corresponding to a fragment previously reported to exhibit dominant negative function. These findings demonstrate that ATM heterozygosity may be associated with enhanced clinical radiation sensitivity and suggest a clinical relevance to this truncation that results in a dominant negative-acting protein.
authors.affiliation: Department of Radiation Medicine, Georgetown University Medical School, Washington, District of Columbia, USA.
authors.forename: S
authors.initials: S
authors.lastname: Varghese
authors.forename: R K
authors.initials: RK
authors.lastname: Schmidt-Ullrich
authors.forename: A
authors.initials: A
authors.lastname: Dritschilo
authors.forename: M
authors.initials: M
authors.lastname: Jung
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D006579:Heterozygote; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics* / Q000528:radiation effects; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics* / Q000528:radiation effects; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases