Gene expression profile at the single cell level of human breast tissues of BRCA1/BRCA2 mutation carriers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA928726 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23254951.fastq.gz | Fastqsanger.gz | |||
| SRR23254952.fastq.gz | Fastqsanger.gz | |||
| SRR23254953.fastq.gz | Fastqsanger.gz | |||
| SRR23254954.fastq.gz | Fastqsanger.gz | |||
| SRR23254955.fastq.gz | Fastqsanger.gz |
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Project description:Gene expression profiles of normal human mammary tissue from BRCA1 mutation carriers, non-BRCA1/2 mutation carriers and normal women. RNA was prepared from normal breast tissue (confirmed by pathology) from reduction mammoplasties (n=5) and prophylactic mastectomies of known BRCA1 (n=7) and non-BRCA1/2 mutation carriers (n=8). non-BRCA1/2 carriers were individuals with a strong family history of breast cancer (kConFab Category 1 (http://www.kconfab.org/Collection/Eligibility.shtml) where no mutation in BRCA1 or BRCA2 has been identified in the family by high sensitivity testing (http://www.kconfab.org/Progress/Sensitivity.shtml) of any individual affected by breast or ovarian cancer. Normal breast samples refer to reduction mammoplasty specimens, where family history is generally not known.
2009-08-01 | GSE17072 | GEO
Project description:Gene expression profiles of normal human mammary tissue from BRCA1 mutation carriers, non-BRCA1/2 mutation carriers and normal women. RNA was prepared from normal breast tissue (confirmed by pathology) from reduction mammoplasties (n=5) and prophylactic mastectomies of known BRCA1 (n=7) and non-BRCA1/2 mutation carriers (n=8). non-BRCA1/2 carriers were individuals with a strong family history of breast cancer (kConFab Category 1 (http://www.kconfab.org/Collection/Eligibility.shtml) where no mutation in BRCA1 or BRCA2 has been identified in the family by high sensitivity testing (http://www.kconfab.org/Progress/Sensitivity.shtml) of any individual affected by breast or ovarian cancer. Normal breast samples refer to reduction mammoplasty specimens, where family history is generally not known. Microarray expression profiles were obtained from whole pre-neoplastic breast tissue from three categories of patient, as described in the summary. Samples were checked for keratin gene expression levels as a marker for epithelium tissue, and a number of samples were removed because two or more keratin genes lacked detectable expression (BeadStudio detection p-value 0.01). One other sample was removed because its expression profile appeared abnormal. Out of 36 samples initially profiled, 20 passed the quality filters and were used for the final analysis.
2009-08-01 | E-GEOD-17072 | biostudies-arrayexpress
Project description:Pathogenic germline mutations in BRCA1 or BRCA2 are detected in less than one third of families with a strong history of breast cancer. It is therefore expected that mutations still remain undetected by currently used screening methods. In addition, a growing number of BRCA1/2 sequence variants of unclear pathogen significance are found in the families, constituting an increasing clinical challenge. New methods are therefore needed to improve the detection rate and aid the interpretation of the clinically uncertain variants. In this study we analyzed a series of 33 BRCA1, 22 BRCA2, and 128 sporadic tumors by RNA profiling to investigate the classification potential of RNA profiles to predict BRCA1/2 mutation status. We found that breast tumors from BRCA1 and BRCA2 mutation carriers display characteristic RNA expression patterns, allowing them to be distinguished from sporadic tumors. The majority of BRCA1 tumors were basal-like while BRCA2 tumors were mainly luminal B. Using RNA profiles, we were able to distinguish BRCA1 tumors from sporadic tumors among basal-like tumors with 83% accuracy and BRCA2 from sporadic tumors among luminal B tumors with 89% accuracy. Furthermore, subtype-specific BRCA1/2 gene signatures were successfully validated in two independent data sets with high accuracies. Although additional validation studies are required, indication of BRCA1/2 involvement (“BRCAness”) by RNA profiling could potentially be valuable as a tool for distinguishing pathogenic mutations from benign variants, for identification of undetected mutation carriers, and for selecting patients sensitive to new therapeutics such as PARP inhibitors. Gene expression profiling of 183 breast tumor samples. Breast tumors from hereditary breast cancer patients carrying a pathogenic BRCA1 (n=33) or BRCA2 (n=22) germ-line mutation were included in the study. Serving as a representative control group, primary breast tumor samples (n=128) were randomly selected. The study was conducted using Agilent-029949 Custom SurePrint G3 Human GE 8x60K Microarray platform. For cross-platform validation, a subset of the tumor samples (92 of the 183 samples) were analyzed by our in-house spotted microarray platform.
2013-06-28 | E-GEOD-40115 | biostudies-arrayexpress
Project description:Pathogenic germline mutations in BRCA1 or BRCA2 are detected in less than one third of families with a strong history of breast cancer. It is therefore expected that mutations still remain undetected by currently used screening methods. In addition, a growing number of BRCA1/2 sequence variants of unclear pathogen significance are found in the families, constituting an increasing clinical challenge. New methods are therefore needed to improve the detection rate and aid the interpretation of the clinically uncertain variants. In this study we analyzed a series of 33 BRCA1, 22 BRCA2, and 128 sporadic tumors by RNA profiling to investigate the classification potential of RNA profiles to predict BRCA1/2 mutation status. We found that breast tumors from BRCA1 and BRCA2 mutation carriers display characteristic RNA expression patterns, allowing them to be distinguished from sporadic tumors. The majority of BRCA1 tumors were basal-like while BRCA2 tumors were mainly luminal B. Using RNA profiles, we were able to distinguish BRCA1 tumors from sporadic tumors among basal-like tumors with 83% accuracy and BRCA2 from sporadic tumors among luminal B tumors with 89% accuracy. Furthermore, subtype-specific BRCA1/2 gene signatures were successfully validated in two independent data sets with high accuracies. Although additional validation studies are required, indication of BRCA1/2 involvement (“BRCAness”) by RNA profiling could potentially be valuable as a tool for distinguishing pathogenic mutations from benign variants, for identification of undetected mutation carriers, and for selecting patients sensitive to new therapeutics such as PARP inhibitors.
2013-06-28 | GSE40115 | GEO
Project description:Goal of this study is to develop the single cell map of breast tissues of women who carry germline mutations in BRCA1 or BRCA2 genes. Towards this goal, we performed single cell RNA sequencing (sc-RNAseq) of cells isolated from cryopreserved tissues.
2024-01-17 | GSE223886 | GEO
Project description:The functional consequences of missense variants in disease genes are difficult to predict. We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutations (BRCAX cases). 72 cell lines from affected women in high-risk breast-ovarian families were assayed after exposure to ionising irradiation, including 23 BRCA1 carriers, 22 BRCA2 carriers, and 27 BRCAX individuals. A subset of 10 BRCAX individuals carried rare BRCA1/2 sequence variants considered to be of low clinical significance (LCS). BRCA1 and BRCA2 mutation carriers had similar expression profiles, with some subclustering of missense mutation carriers. The majority of BRCAX individuals formed a distinct cluster, but BRCAX individuals with LCS variants had expression profiles similar to BRCA1/2 mutation carriers. Gaussian Process Classifier predicted BRCA1, BRCA2 and BRCAX status with a maximum of 62% accuracy, and prediction accuracy decreased with inclusion of BRCAX samples carrying an LCS variant, and inclusion of pathogenic missense carriers. Similarly, prediction of mutation status with gene lists derived using Support Vector Machines was good for BRCAX samples without an LCS variant (82-94%), poor for BRCAX with an LCS (40-50%), and improved for pathogenic BRCA1/2 mutation carriers when the gene list used for prediction was appropriate to mutation effect being tested (71-100%). This study indicates that mutation effect, and presence of rare variants possibly associated with a low risk of cancer, must be considered in the development of array-based assays of variant pathogenicity. Keywords: cell type comparison, stress response
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Project description:Early genetic changes during cancer initiation may provide targets for agents that delay, or even prevent, cancer. We hypothesized that cells bearing a single inherited âhitâ in a tumor suppressor gene express an altered mRNA repertoire that may identify targets for measures that could delay or even prevent progression to carcinoma. Here, we report on the transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1 and BRCA2 mutation-carriers and controls. Our comparison analyses identified multiple changes in gene expression, in both tissues for both mutations that were independently validated by real-time RT-PCR analysis. Several of the differentially expressed genes had been previously proposed as cancer markers including, mammaglobin in breast cancer and serum amyloid in ovarian cancer. These findings demonstrate that heterozygosity for a mutant tumor suppressor gene can alter the expression profiles of phenotypically normal epithelial cells in a gene-specific manner, and that these detectable effects of âone-hitâ represent early molecular changes in tumorigenesis that may serve as novel biomarkers of cancer risk and as targets for chemoprevention Using affymetrix U133 plus2 chips, we compare the transcriptome of primary breast and ovarian epithelial cultures derived from subjects predisposed to cancer, bearing monoallelic BRCA1 or BRCA2 mutations, with corresponding cultures from control individuals that do not have mutations. For both breast and ovarian samples, epithelial cell cultures were generated from 6 subjects that have both BRCA1 or BRCA2 mutations and 6 subjects that do not have mutations. Affymetrix U133 plus 2 chips were used to profile the transcriptome of BRCA1 or BRCA2 mutant and wild type. In total 36 chips were used to profile 18 samples from both breast and ovary, 6 mutant (BRCA1 and BRCA2) and 6 wild type.
2010-03-07 | E-GEOD-19383 | biostudies-arrayexpress
Project description:Approximately 5% of all breast cancers can be attributed to an inherited mutation in one of two cancer susceptibility genes, BRCA1 and BRCA2. We searched for genes that have the potential to distinguish healthy BRCA1 and BRCA2 mutation carriers from non-carriers based on differences in expression profiling. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers. We identified 137 probe sets in BRCA1 carriers and 1345 in BRCA2 carriers with differential gene expression. Gene Ontology analysis revealed that most of these genes relate to regulation pathways of DNA repair processes, cell cycle regulation and apoptosis. Real-time PCR was performed on the 36 genes which were most prominently differentially expressed in the microarray assay; 21 genes were shown to be significantly differentially expressed in BRCA1 or BRCA2 mutation carriers as compared to controls (p<0.05). Based on a validation study with 40 mutation carriers and 17 non-carriers, a multiplex model that included six or more coincidental genes of 18 selected genes was constructed in order to predict the risk of carrying a mutation. The results using this model showed sensitivity 95% and specificity 88%. In summary, our study provides insight into the biological effect of heterozygous mutations in BRCA1 and BRCA2 genes in response to ionizing irradiation induced DNA damage. We also suggest a set of 18 genes that can be used as a prediction and screening tool for BRCA1 or BRCA2 mutational carriers by using easily obtained lymphocytes. Using expression microarrays we compared gene expression of irradiated lymphocytes from BRCA1 and BRCA2 mutation carriers versus control non-carriers Fresh blood samples were obtained from 9 BRCA1 and 8 BRCA2 mutation carriers and 9 mutation-negative women. Lymphocytes were collected from fresh blood samples, and RNA was extracted one hour after γ-irradiation
2013-01-10 | E-GEOD-39976 | biostudies-arrayexpress
Project description:Female BRCA1 mutation carriers have a nearly 80% probability of developing breast cancer during their life-time. We hypothesized that the breast epithelium at risk in BRCA1 mutation carriers harbors mammary epithelial cells (MECs) with altered proliferation and differentiation properties. Microarray studies revealed that PMEC colonies from BRCA1 mutation carriers anticipate expression profiles found in BRCA1-related tumors, and that the EGFR pathway is upregulated in BRCA1 mutation carriers compared ton non BRCA1 mutation carriers. Keywords: Class comparison and pathway analysis
2008-11-20 | GSE13671 | GEO
Project description:Female BRCA1 mutation carriers have a nearly 80% probability of developing breast cancer during their life-time. We hypothesized that the breast epithelium at risk in BRCA1 mutation carriers harbors mammary epithelial cells (MECs) with altered proliferation and differentiation properties. Microarray studies revealed that PMEC colonies from BRCA1 mutation carriers anticipate expression profiles found in BRCA1-related tumors, and that the EGFR pathway is upregulated in BRCA1 mutation carriers compared ton non BRCA1 mutation carriers. Keywords: Class comparison and pathway analysis 10 colonies were collected and RNA was isolated using the Absolutely RNA Nanoprep kit, Stratagene. The arrays included duplicates from four normal controls and from two BRCA1 mutation carriers and single arrays from another two BRCA1 mutation carriers.
2008-11-19 | E-GEOD-13671 | biostudies-arrayexpress