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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

«15 BRCA1 mutation carriers versus 15 non-carriers» were subjected to hierarchical clustering in both the experiment and the gene dimensions using the 133 differentially expressed genes. Branches are color coded according to the BRCA1 mutation status of each sample. Blue, non-carriers; Yellow, BRCA1 mutation carriers.
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f3-cin-07-41: «15 BRCA1 mutation carriers versus 15 non-carriers» were subjected to hierarchical clustering in both the experiment and the gene dimensions using the 133 differentially expressed genes. Branches are color coded according to the BRCA1 mutation status of each sample. Blue, non-carriers; Yellow, BRCA1 mutation carriers.

Mentions: Hierarchical clustering in both gene and experiment dimensions using these 133 genes (Fig. 3) showed two main clusters with a positive predictive value of 100% and a negative predictive value of 80%. The dendogram branches show eleven of the 15 BRCA1 mutation carriers grouped together in a first cluster, while the second cluster contains three subgroups in which four BRCA1 mutation carriers are misclassified with non-carriers. These four samples were not distinguishable from other BRCA1 mutation carriers by their gender, age, diagnosis, BRCA1 mutation type or by the functional domain affected by the mutation. None of their characteristics allowed us to exclude them from further analysis.


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)

«15 BRCA1 mutation carriers versus 15 non-carriers» were subjected to hierarchical clustering in both the experiment and the gene dimensions using the 133 differentially expressed genes. Branches are color coded according to the BRCA1 mutation status of each sample. Blue, non-carriers; Yellow, BRCA1 mutation carriers.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-cin-07-41: «15 BRCA1 mutation carriers versus 15 non-carriers» were subjected to hierarchical clustering in both the experiment and the gene dimensions using the 133 differentially expressed genes. Branches are color coded according to the BRCA1 mutation status of each sample. Blue, non-carriers; Yellow, BRCA1 mutation carriers.
Mentions: Hierarchical clustering in both gene and experiment dimensions using these 133 genes (Fig. 3) showed two main clusters with a positive predictive value of 100% and a negative predictive value of 80%. The dendogram branches show eleven of the 15 BRCA1 mutation carriers grouped together in a first cluster, while the second cluster contains three subgroups in which four BRCA1 mutation carriers are misclassified with non-carriers. These four samples were not distinguishable from other BRCA1 mutation carriers by their gender, age, diagnosis, BRCA1 mutation type or by the functional domain affected by the mutation. None of their characteristics allowed us to exclude them from further analysis.

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