The Importance of ATM Mutations and Polymorphisms in Breast Cancer and Radiation Sensitivity
Abstract
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 and found 4 repetitive single-base genetic variants in the ATM cDNA. We then compared the frequency of these variants to that of a control set of samples from 996 individuals without cancer. We found that a Ser49Cys variant was more commonly represented in the breast cancer patients (6.%% vs 1.3%, p=O.006). In addition, we found that a Prol954Arg variant was more common in a group of 27 Caucasian patients who experienced a significant normal tissue injury after radiation treatments compared to the Caucasian controls (18.5% vs 6.6%, p=O.037) - We also developed an in vitro assay that isolated protein complexes that bind double-strand breaks in order to study the role of ATM protein in double-strand break repair. We identified that ATM and at least ten other proteins make up a clinically relevant protein complex. We found that the amount of this complex in both normal and tumor cells strongly correlated with their radiosensitivity. We feel this assay may prove to have significant clinical relevance as a predictor of both tumor and host radiosensitivity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA424001
Entities
People
- Thomas A. Buchholz
Organizations
- The University of Texas MD Anderson Cancer Center