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%) cell lines showed markedly reduced ATM kinase activity, despite normal level of expression of ATM protein. DNA from the index cases with aberrant ATM kinase activity is currently being screened by D-HPLC to determine whether the lack of activity is due to mutations in AIM. Pathogenic ATM mutations (T7271G, IVS 10 6T-G) have been constructed in expression vectors. Functional analysis has been performed for V2424G (base T7271G).
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA416707
Entities
People
- George Chenevix-trench
- Kum K. Khanna
- Sean Grimmond
Organizations
- QIMR Berghofer Medical Research Institute