A Novel Method to Screen for Dominant Negative ATM Mutations in Familial Breast Cancer

Abstract

The aim of this proposal is to identify families carrying potentially pathogenic AIM mutations by assaying for ATM kinase activity in cell lines derived from individuals with multiple cases of breast cancer in their family but no pathogenic BRCA or BRCA2 mutation ('BRCAx' families). If pathogenic mutations in AIM are found in these families it will substantiate the role of AIM in breast cancer susceptibility, allow us to characterize the functional effects of those mutations, and provide clinically valuable information for the families involved. We have analyzed 145 cell lines established from index cases from non-BRCAl/2 breast cancer families for ATM expression and activity. 10/145 (6.9%) ..