ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer
Annual rept. 1 Jul 2004-30 Jun 2005
MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
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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. The main accomplishments during the past year were accrual and complete DHPLC screening of the ATM gene for additional subjects as well as the performance of functional studies with a series of patient derived cell lines to measure radiosensitivity, ATM protein levels and p53 phosphorylation by ATM.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research