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

The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced RTOG/EORTC grade 3/4 subcutaneous late tissue morbidity possess a mutated ATM gene compared with patients who do not suffer these complications. An additional objective is to determine the functional impact upon the protein encoded both in the ATM gene for each mutation identified and subsequent cellular radiosensitivity, The specific aims of this project are to (1) screen 50 breast cancer patients for a ATM mutations who developed radiation-induced grade 3/4 late subcutaneous tissue morbidity as defined by the RTOG/EORTC scoring scheme, (2) establish 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 mutation identified affect radiosensitivity and normal activity of the protein produced by the ATM gene.