NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE17764 Query DataSets for GSE17764
Status Public on Jan 20, 2010
Title Expression profiles associated with BRCA1 and BRCA2 mutation status in familial breast cancer patients
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Use of DNA damaging agents and RNA pooling to assess expression profiles associated with BRCA1 and BRCA2 mutation status in familial breast cancer patients

Background: A large number of rare sequence variants of unknown clinical significance have been identified in the breast cancer susceptibility genes, BRCA1 and BRCA2. Determining the functional effect of these variants as well as their role in breast cancer susceptibility can be challenging using current classification methods. Methodology/Principal Findings: To identify predictors of pathogenic mutation status in familial breast cancer patients, we explored the use of gene expression arrays to assess the effect of two DNA damaging agents (irradiation and mitomycin C) on cellular response in relation to BRCA1 and BRCA2 mutation status. A range of regimes were used to treat 27 lymphoblastoid cell-lines (LCLs) derived from affected women in high-risk breast cancer families (nine BRCA1, nine BRCA2, and nine non-BRCA1/2 or BRCAX individuals) and nine LCLs from healthy individuals. Using an RNA pooling strategy, we found that treating LCLs with 1.2 μM mitomycin C and measuring the gene expression profiles 1 hour post-treatment had the greatest potential to discriminate BRCA1, BRCA2 and BRCAX mutation status. A classifier was built using the expression profile of nine QRT-PCR validated genes that were associated with BRCA1, BRCA2 and BRCAX status in RNA pools. These nine genes could distinguish BRCA1 from BRCA2 carriers with 83% accuracy in individual samples, but three-way analysis for BRCA1, BRCA2 and BRCAX had a maximum of 59% prediction accuracy. Conclusions/Significance: Our results suggest that, compared to BRCA1 and BRCA2 mutation carriers, non-BRCA1/2 (BRCAX) individuals are genetically heterogeneous. This study also demonstrates the effectiveness of RNA pools to compare the expression profiles of cell-lines from BRCA1, BRCA2 and BRCAX cases after treatment with irradiation and mitomycin C as a method to prioritize treatment regimes for detailed downstream expression analysis.
 
Overall design Total RNA was isolated from 27 lymphoblastoid cell-lines (LCLs) derived from affected women in high-risk breast cancer families (nine BRCA1, nine BRCA2, and nine non-BRCA1/2 women) and nine LCLs from healthy women. LCLs from each of the BRCA1, BRCA2 and BRCAX patient groups, and from healthy controls, were irradiated at 10 Gy using a calibrated Cesium-137 source or treated with MMC at two different doses (0.4 µM or 1.2 µM). Cells were harvested prior to IR or MMC treatment (T0), at 1 h after IR exposure, and at 1 and 2 h after exposure for MMC.
 
Contributor(s) Walker LC, Spurdle AB
Citation(s) 20174566
Submission date Aug 21, 2009
Last update date Jan 18, 2013
Contact name Logan Walker
E-mail(s) logan.walker@qimr.edu.au
Organization name Queensland Institute of Medical Research
Street address PO RBH
City Brisbane
State/province QLD
ZIP/Postal code 4029
Country Australia
 
Platforms (1)
GPL6104 Illumina humanRef-8 v2.0 expression beadchip
Samples (72)
GSM443686 60 min post-10 Gy IR 4098316045_D_IR_BRCA1_Pool 1
GSM443687 60 min post-0.4uM Mitomycin C 4098316045_E_MMC1_BRCA1_Pool 1
GSM443688 60 min post-1.2uM Mitomycin C 4098316045_F_MMC2_BRCA1_Pool 1
Relations
BioProject PRJNA118311

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE17764_RAW.tar 3.4 Mb (http)(custom) TAR
GSE17764_non_normalized.txt.gz 6.0 Mb (ftp)(http) TXT
Processed data included within Sample table
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap