Enhanced radiation late effects and cellular radiation sensitivity in an ATM heterozygous breast cancer patient

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 t runcation test (PTT) and sequence analysis identified a truncation within t he leucine zipper domain, corresponding to a fragment previously reported t o exhibit dominant negative function. These findings demonstrate that ATM h eterozygosity may be associated with enhanced clinical radiation sensitivit y and suggest a clinical relevance to this truncation that results in a dom inant negative-acting protein. Radiat. Oncol. Invest. 7:231-237, 1999. (C) 1999 Wiley-Liss, Inc.