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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

Mean of CY5 processed signal over 30 experiments for selected BRCA1-interacting proteins and transcriptional targets.
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f1-cin-07-41: Mean of CY5 processed signal over 30 experiments for selected BRCA1-interacting proteins and transcriptional targets.

Mentions: Signal intensity in lymphocytes was low. Although the dynamic range for the red and green channels was wide (from 30 to 60,000 for net signals), the median intensities were around 80 for both channels. As presented in Figure 1, the average BRCA1 signal, and therefore expression, was very low. The second major susceptibility gene involved in breast cancer risk, BRCA2, was not significantly expressed in PBMCs. Among transcripts coding for BRCA1-interacting proteins, transcriptional regulation proteins were more highly represented than those involved in DNA damage repair or cell cycle checkpoints. Proteins related to estrogen signaling (androgen and estrogen receptors) were not significantly expressed. Most of the known transcriptional targets of BRCA1 were well represented.


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)

Mean of CY5 processed signal over 30 experiments for selected BRCA1-interacting proteins and transcriptional targets.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-cin-07-41: Mean of CY5 processed signal over 30 experiments for selected BRCA1-interacting proteins and transcriptional targets.
Mentions: Signal intensity in lymphocytes was low. Although the dynamic range for the red and green channels was wide (from 30 to 60,000 for net signals), the median intensities were around 80 for both channels. As presented in Figure 1, the average BRCA1 signal, and therefore expression, was very low. The second major susceptibility gene involved in breast cancer risk, BRCA2, was not significantly expressed in PBMCs. Among transcripts coding for BRCA1-interacting proteins, transcriptional regulation proteins were more highly represented than those involved in DNA damage repair or cell cycle checkpoints. Proteins related to estrogen signaling (androgen and estrogen receptors) were not significantly expressed. Most of the known transcriptional targets of BRCA1 were well represented.

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