The Importance of ATM Mutations and Polymorphisms in Breast Cancer and Radiation Sensitivity
Annual summary rept. 1 Oct 2000-30 Sep 2001
M D ANDERSON CANCER CENTER HOUSTON TX
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The objective of my 4-year Career Development Award was to determine whether ATM heterozygosity contributes to breast cancer development and radiation injury. We sequenced the ATM cDNA of 93 breast cancer patients, 22 of whom experienced a normal tissue injury from radiation treatment. We found that none of these patients had an ATM mutation that resulted in a protein truncation. This finding is consistent with publications from others. We did identify 3 repetitive single-base changes in the ATM cDNA that may represent missense mutations. We then compared the frequency of these single- base changes between the breast cancer patients and a control set of samples from 996 individuals without cancer. We found that one of these single-base changes was more commonly represented in the breast cancer patients 6.7 vs 1.6, p0.006 . To further assess whether this base change results in a functional consequence, we developed an in vitro assay to study the role the ATM protein plays in repair of double-strand DNA damage. We now plan to study cells with the identified single-base changes using this assay. We hypothesize that these single base changes affect a cellular phenotype previously shown to have relevance to breast cancer development and radiation injury risk.
- Medicine and Medical Research