ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

摘要

The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared with patients who do not suffer these complications. An additional objective is to determine the functional impact upon the protein encoded by the ATM gene for each genetic alteration identified and subsequent cellular radiosensitivity. The specific aims of this project are to (1) screen 50 breast cancer patients for ATM genetic alterations who developed radiation induced late subcutaneous tissue morbidity (2) establish a control group and screen 100 patients without evidence of this late radiation reaction and (3) perform functional studies using cells from patients identified as ATM carriers to determine to what extent each ATM variant identified affects radiosensitivity and normal activity of the protein produced by the ATM gene.