title: Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia.
abstract: BACKGROUND
  Severe early and late radiation reaction to radiotherapy is extremely rare in breast cancer patients. Such a reaction prompted an investigation into a 44-year-old mother (patient A-T213).
  
  
  METHODS
  A neurological examination was performed and blood lymphocytes and skin fibroblasts were assessed for radiosensitivity chromosomally and by colony-forming assay. The ATM gene was sequenced and ATM mutations modelled by site-directed mutagenesis. The ATM kinase activity was also assessed.
  
  
  RESULTS
  Patient A-T213 was normally ambulant with no ataxia and minimal other neurological features. T lymphocytes and skin fibroblasts were unusually radiosensitive, although less sensitive than in classical ataxia telangiectasia (A-T). A lymphoblastoid cell line and skin fibroblasts expressed ATM protein with some retained kinase activity. One missense ATM mutation c.8672G>A (p.Gly2891Asp) and a c.1A>G substitution were identified. In the modelling system, the p.Gly2891Asp mutant protein was expressed and shown to have residual ATM kinase activity.
  
  
  CONCLUSIONS
  Patient A-T213 has a milder form of A-T with biallelic ATM mutations, which may have contributed to breast cancer development, and certainly caused the severe radiation reaction. Ataxia telangiectasia should be investigated as a potential cause of untoward severe early and late radiation reactions in breast cancer patients.
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Byrd
authors.forename: V
authors.initials: V
authors.lastname: Srinivasan
authors.forename: J I
authors.initials: JI
authors.lastname: Last
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Biggs
authors.forename: E F
authors.initials: EF
authors.lastname: Carney
authors.forename: A
authors.initials: A
authors.lastname: Exley
authors.forename: C
authors.initials: C
authors.lastname: Abson
authors.forename: G S
authors.initials: GS
authors.lastname: Stewart
authors.forename: L
authors.initials: L
authors.lastname: Izatt
authors.forename: A M
authors.initials: AM
authors.lastname: Taylor
mesh_terms: D001260:Ataxia Telangiectasia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics / Q000532:radiotherapy*; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011836:Radiation Tolerance; 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