S Varghese, R K Schmidt-Ullrich, A Dritschilo, M Jung
{"title":"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","doi":"10.1002/(SICI)1520-6823(1999)7:4<231::AID-ROI4>3.0.CO;2-S","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20894,"journal":{"name":"Radiation oncology investigations","volume":"7 4","pages":"231-7"},"PeriodicalIF":0.0000,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/(SICI)1520-6823(1999)7:4<231::AID-ROI4>3.0.CO;2-S","citationCount":"22","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiation oncology investigations","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/(SICI)1520-6823(1999)7:4<231::AID-ROI4>3.0.CO;2-S","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 22
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.