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

✍ Scribed by Susan Varghese; Rupert K. Schmidt-Ullrich; Anatoly Dritschilo; Mira Jung

• Book ID: 102661315
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 577 KB
• Volume: 7
• Category: Article
• ISSN: 1065-7541
• DOI: 10.1002/(sici)1520-6823(1999)7:4<231::aid-roi4>3.0.co;2-s

✦ Synopsis

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.