Radiation Oncology/Cancer Syndromes/Ataxia-Telangiectasia


Overview edit

  • Absence of ATM protein (90% none, 10% trace, 1% present but non-functional), by immunoblotting
  • Progressive cerebellar ataxia (starting age 1-4), oculomotor apraxia, choreoathetosis, frequent infections, telangiectasias of the conjunctivae, immunodeficiency, and an increased risk for malignancy.
  • Cancer risk:
    • Homozygotes: life-time risk 40%
      • Leukemia and lymphoma account for ~85%
      • With longer life-span, also ovarian, breast, gastric, melanoma, leiomyomas, and sarcomas
    • Heterozygotes: risk 4x normal population
      • Majority of increase due to breast cancer
  • Autosomal recessive
  • Sensitivity to ionizing radiation; but no increased sensitivity to UV light
  • Cells don't arrest in S phase after DNA damage
  • Alpha-fetoprotein elevated in 95%

Radiation Therapy Literature edit

  • Severe response to ionizing radiation in patients with AT
  • Some ATM variants may be predictive of adverse RT responses


  • 1968 PMID 5687489 -- "Radiation reaction in ataxia telangiectasia." (Morgan JL, Am J Dis Child. 1968 Nov;116(5):557-8.)
  • 1967 PMID 6072741 -- "Ataxia telangiectasia. Neoplasia, untoward response to x-irradiation, and tuberous sclerosis." (Gotoff SP, Am J Dis Child. 1967 Dec;114(6):617-25.)

ATM variants

  • Aarhus; 2006 (Denmark) PMID 16338099 -- "ATM sequence variants and risk of radiation-induced subcutaneous fibrosis after postmastectomy radiotherapy." (Andreassen CN, Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):776-83.)
    • Conclusion: ATM codon 1853 may be associated with development of Grade 3 fibrosis in breast RT
  • Mt. Sinai, NY
    • 2007 PMID 17517479 -- "Possession of ATM Sequence Variants as Predictor for Late Normal Tissue Responses in Breast Cancer Patients Treated With Radiotherapy." (Ho AY, Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):677-84.)
      • Conclusion: Sequence variants in ATM may predict for late response in breast CA
    • 2002 PMID 11849780 -- "ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects." (Ianuzzi CM, Int J Radiat Oncol Biol Phys. 2002 Mar 1;52(3):606-13.)
      • Conclusion: Significant correlation between ATM mutations and Grade 3-4 fibrosis