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Use of gene expression profiles of peripheral blood lymphocytes to distinguish BRCA1 mutation carriers in high risk breast cancer families.

Vuillaume ML, Uhrhammer N, Vidal V, Vidal VS, Chabaud V, Jesson B, Kwiatkowski F, Bignon YJ - Cancer Inform (2009)

Bottom Line: Statistical analysis revealed a slight tendency for 133 genes to be differentially expressed between BRCA1 mutation carriers and non-carriers.However, hierarchical clustering of these genes did not accurately discriminate BRCA1 mutation carriers from non-carriers.Expression variation for these genes according to BRCA1 mutation status was weak.

View Article: PubMed Central - PubMed

Affiliation: Département d'Oncogénétique, Centre Jean Perrin, Clermont-Ferrand, France.

ABSTRACT
Mutations in two major genes, BRCA1 and BRCA2, account for up to 30% of families with hereditary breast cancer. Unfortunately, in most families there is little to indicate which gene should be targeted first for mutation screening, which is labor intensive, time consuming and often prohibitively expensive. As BRCA1 is a tumor suppressor gene involved in various cellular processes, heterozygous mutations could deregulate dependent pathways, such as DNA damage response, and disturb transcriptional activity of genes involved in the downstream signaling cascade. We investigated gene expression profiling in peripheral blood lymphocytes to evaluate this strategy for distinguishing BRCA1 mutation carriers from non-carriers. RNA from whole blood samples of 15 BRCA1 mutation carriers and 15 non-carriers from BRCA1 or BRCA2 families were hybridized to Agilent Technologies Whole Human Genome OligoMicroarrays (4 x 44 K multiplex format) containing 41,000 unique human genes and transcripts. Gene expression data were analyzed with Welch's t-tests and submitted to hierarchical clustering (GeneSpring GX software, Agilent Technologies). Statistical analysis revealed a slight tendency for 133 genes to be differentially expressed between BRCA1 mutation carriers and non-carriers. However, hierarchical clustering of these genes did not accurately discriminate BRCA1 mutation carriers from non-carriers. Expression variation for these genes according to BRCA1 mutation status was weak. In summary, microarray profiling of untreated whole blood does not appear to be informative in identifying breast cancer risk due to BRCA1 mutation.

No MeSH data available.


Related in: MedlinePlus

Hierarchical clustering performed on all samples «15 BRCA1 mutation carriers versus 15 non-carriers» in both the experiment and the gene dimensions using a pre-screened list of 16,997 genes. Branches are color coded according to the family number of each sample.
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f2-cin-07-41: Hierarchical clustering performed on all samples «15 BRCA1 mutation carriers versus 15 non-carriers» in both the experiment and the gene dimensions using a pre-screened list of 16,997 genes. Branches are color coded according to the family number of each sample.

Mentions: The mutation carrier and non-carrier samples were cohybridized with an internal reference to Agilent 44 K Whole Human genome Oligo Microarrays. Data were normalized using Feature Extraction software (Agilent Technologies, Palo Alto, CA) and analyzed with Genespring GX software (Agilent Technologies, Palo Alto, CA), resulting in a pre-screened set of 16,997 genes. An unsupervised method was used to reveal distinct clusters according to different parameters, such as BRCA1 mutation status, gender, age or diagnosis. Average linkage clustering analysis using Euclidean distance was performed in both gene and experiment dimensions. This analysis did not show any clear subgroup of samples with similar expression patterns that associated with BRCA1 mutation status (Fig. 2). The two main clusters observed in this dendogram were not associated with any of the parameters described above (family number, gender, age, diagnosis, BRCA1 mutation status). Some samples from the same family grouped together (three samples from family 2001: R673–R674–R683 and two samples from family 1541: R443–R609) regardless of gender or BRCA1 mutation status, although other samples from the same family were distant in the clustering.


Use of gene expression profiles of peripheral blood lymphocytes to distinguish BRCA1 mutation carriers in high risk breast cancer families.

Vuillaume ML, Uhrhammer N, Vidal V, Vidal VS, Chabaud V, Jesson B, Kwiatkowski F, Bignon YJ - Cancer Inform (2009)

Hierarchical clustering performed on all samples «15 BRCA1 mutation carriers versus 15 non-carriers» in both the experiment and the gene dimensions using a pre-screened list of 16,997 genes. Branches are color coded according to the family number of each sample.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2664702&req=5

f2-cin-07-41: Hierarchical clustering performed on all samples «15 BRCA1 mutation carriers versus 15 non-carriers» in both the experiment and the gene dimensions using a pre-screened list of 16,997 genes. Branches are color coded according to the family number of each sample.
Mentions: The mutation carrier and non-carrier samples were cohybridized with an internal reference to Agilent 44 K Whole Human genome Oligo Microarrays. Data were normalized using Feature Extraction software (Agilent Technologies, Palo Alto, CA) and analyzed with Genespring GX software (Agilent Technologies, Palo Alto, CA), resulting in a pre-screened set of 16,997 genes. An unsupervised method was used to reveal distinct clusters according to different parameters, such as BRCA1 mutation status, gender, age or diagnosis. Average linkage clustering analysis using Euclidean distance was performed in both gene and experiment dimensions. This analysis did not show any clear subgroup of samples with similar expression patterns that associated with BRCA1 mutation status (Fig. 2). The two main clusters observed in this dendogram were not associated with any of the parameters described above (family number, gender, age, diagnosis, BRCA1 mutation status). Some samples from the same family grouped together (three samples from family 2001: R673–R674–R683 and two samples from family 1541: R443–R609) regardless of gender or BRCA1 mutation status, although other samples from the same family were distant in the clustering.

Bottom Line: Statistical analysis revealed a slight tendency for 133 genes to be differentially expressed between BRCA1 mutation carriers and non-carriers.However, hierarchical clustering of these genes did not accurately discriminate BRCA1 mutation carriers from non-carriers.Expression variation for these genes according to BRCA1 mutation status was weak.

View Article: PubMed Central - PubMed

Affiliation: Département d'Oncogénétique, Centre Jean Perrin, Clermont-Ferrand, France.

ABSTRACT
Mutations in two major genes, BRCA1 and BRCA2, account for up to 30% of families with hereditary breast cancer. Unfortunately, in most families there is little to indicate which gene should be targeted first for mutation screening, which is labor intensive, time consuming and often prohibitively expensive. As BRCA1 is a tumor suppressor gene involved in various cellular processes, heterozygous mutations could deregulate dependent pathways, such as DNA damage response, and disturb transcriptional activity of genes involved in the downstream signaling cascade. We investigated gene expression profiling in peripheral blood lymphocytes to evaluate this strategy for distinguishing BRCA1 mutation carriers from non-carriers. RNA from whole blood samples of 15 BRCA1 mutation carriers and 15 non-carriers from BRCA1 or BRCA2 families were hybridized to Agilent Technologies Whole Human Genome OligoMicroarrays (4 x 44 K multiplex format) containing 41,000 unique human genes and transcripts. Gene expression data were analyzed with Welch's t-tests and submitted to hierarchical clustering (GeneSpring GX software, Agilent Technologies). Statistical analysis revealed a slight tendency for 133 genes to be differentially expressed between BRCA1 mutation carriers and non-carriers. However, hierarchical clustering of these genes did not accurately discriminate BRCA1 mutation carriers from non-carriers. Expression variation for these genes according to BRCA1 mutation status was weak. In summary, microarray profiling of untreated whole blood does not appear to be informative in identifying breast cancer risk due to BRCA1 mutation.

No MeSH data available.


Related in: MedlinePlus