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Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient.
Authors:S Varghese  R K Schmidt-Ullrich  A Dritschilo  M Jung
Affiliation:Department of Radiation Medicine, Georgetown University Medical School, Washington, District of Columbia, USA.
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.
Keywords:
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