Role of the ATM Gene in Bilateral Breast Cancer Following Radiotherapy

摘要

The purpose of this project was to screen women who developed either unilateral or bilateral breast cancer for mutations and polymorphisms in the ATM gene. To accomplish this, during the first three years of this project, DNA samples were isolated from breast cancer patients and screened using a Non- radioisotopic RNase Cleavage- based Assay (NIRCA). However, not a single mutation was discovered from any of these patients which raised a concern as to the sensitivity of this assay. To address this concern, the P of this project purchased an instrument for the performance of denaturing high performance liquid chromatography (DHPLC). This is a high throughput technique in which large numbers of DNA samples can be rapidly screened with a high degree of sensitivity and accuracy. During the fourth year of this study, representing a no-cost extension of this project, it was possible to re- screen all of the DNA samples obtained from the unilateral breast cancer patients for ATM mutations using DHPLC. Through this work, we identified 6 breast cancer patients possessing a total of 8 different germline mutations and 43 patients harboring a total of 141 DNA sequence variations representing 21 different common polymorphisms and rare variants.