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 A TM 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 BR CA1 or BRCA2 mutation (BRCAx' families). We have analysed 252 cell lines established from index cases from BRCAx families for ATM expression and activity. Overall, analysis of the data suggests that impaired activation of ATM can not be used as a screening tool to identify families that carry dominant negative mutation in ATM due to natural variation amongst LCLs. Microarrays have been performed to determine differences in gene expression between heterozygotes or homozygotes for the T7271G mutation against each other and wild type control pools. These data have suggested candidate genes that are altered in their expression in ATMmutation carriers. The validation of this data in carriers of different ATM mutation indicated that the heterozygous carriers of T7271G mutation display a gene expression phenotype that appears identical to carriers of protein truncating mutations in ATM, suggesting that the expression signature may not be specific for this particular mutation in ATM but rather can be used to assess the downstream effects of any germ-line change in the ATM gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436939
Entities
People
- Georgia Chenevix-Trench
- Kum K. Khanna
- Sean Grimmond
Organizations
- QIMR Berghofer Medical Research Institute