Gene expression profiling after radiation-induced DNA damage is strongly predictive of BRCA1 mutation carrier status
| Autor: | Colin Campbell, Ros Eeles, Richard D. Williams, Robert TePoele, Ian Giddings, Barry A. Gusterson, Gerald Gui, John H. Peacock, Zsofia Kote-Jarai, Nicola Cattini, Richard Wooster, Maria Copeland, Paul Workman |
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| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
Heterozygote DNA Complementary DNA damage Genes BRCA1 Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Biology Protein Serine-Threonine Kinases Complementary DNA Gene expression Cluster Analysis Humans Gene Oligonucleotide Array Sequence Analysis Genetics Tumor Suppressor Proteins Fibroblasts Molecular biology Gene expression profiling DNA-Binding Proteins Gene Expression Regulation Neoplastic Oncology Mutation (genetic algorithm) Significance analysis of microarrays Mutation Gene chip analysis Female Rad51 Recombinase Cyclin-Dependent Kinase Inhibitor p27 DNA Damage |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 10(3) |
| ISSN: | 1078-0432 |
| Popis: | Purpose: The impact of the presence of a germ-line BRCA1 mutation on gene expression in normal breast fibroblasts after radiation-induced DNA damage has been investigated. Experimental Design: High-density cDNA microarray technology was used to identify differential responses to DNA damage in fibroblasts from nine heterozygous BRCA1 mutation carriers compared with five control samples without personal or family history of any cancer. Fibroblast cultures were irradiated, and their expression profile was compared using intensity ratios of the cDNA microarrays representing 5603 IMAGE clones. Results: Class comparison and class prediction analysis has shown that BRCA1 mutation carriers can be distinguished from controls with high probability (∼85%). Significance analysis of microarrays and the support vector machine classifier identified gene sets that discriminate the samples according to their mutation status. These include genes already known to interact with BRCA1 such as CDKN1B, ATR, and RAD51. Conclusions: The results of this initial study suggest that normal cells from heterozygous BRCA1 mutation carriers display a different gene expression profile from controls in response to DNA damage. Adaptations of this pilot result to other cell types could result in the development of a functional assay for BRCA1 mutation status. |
| Databáze: | OpenAIRE |
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