Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA385930 | ENA |
REPOSITORIES: ENA
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Project description:Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis. The purpose of this study was to identify candidate genes possibly involved in pathogenesis of serous ovarian cancer by carrying out a microarray analysis of differentially expressed genes in BRCA1/2- mutation positive ovarian and fallopian tube epithelium derived from RRSO surgery. Freshly frozen ovarian and fallopian tube samples from nine BRCA1/2 mutation carriers scheduled for RRSO were prospectively collected in comparison with five mutation-negative control patients undergoing salpingo-oophorectomy for benign indications. Microarray analysis of genome-wide gene expression was performed on ovarian and fallopian tube samples from BRCA1/2 and control patients. The validation of microarray data was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in selected cases of RRSO samples, and also high grade serous carcinoma samples collected from patients with BRCA phenotype. From 22,733 genes, 454 transcripts were identified that were differentially expressed in BRCA1/2 mutation carriers when statistically compared to controls pooling all ovarian and fallopian tube samples together. Of these, 299 genes were statistically significantly downregulated and 155 genes were upregulated. Differentially expressed genes in BRCA1/2 samples reported here might be involved in serous ovarian carcinogenesis and provide interesting targets for further studies. Both fallopian tube and ovarian samples were collected from each BRCA1/2 mutation carrier resulting in eighteen mutation positive adnexal samples. Both fallopian tube and ovarian control samples were collected from one control patient while either ovarian or fallopian tube sample was available from four control patients, respectively, resulting in 6 adnexal control samples. High quality RNA was available from nine BRCA1/2-mutation positive ovarian and eight BRCA1/2-mutation positive fallopian tube samples and from three control ovarian and three control fallopian tube samples.
2015-02-28 | E-GEOD-66387 | biostudies-arrayexpress
Project description:Microarrays were used to examine gene expression changes that may be present in the fallopian tube epithelium of morphologically normal BRCA1 mutation positive and negative subjects. Fallopian tube epithelia has been implicated as an early point of origin for serous carcninoma. By examining the early events present in the microenvironment of this tissue between BRCA1 mutation carriers and non-carriers, we hoped to elucidate mechanisms that may lead to the development of epithelial ovarian cancer. Laser microcapture of samples from 12 BRCA1 mutation carriers and 12 non-mutation subjects was performed. Samples were further grouped according to menstrual cycle.
2011-04-28 | E-GEOD-28044 | biostudies-arrayexpress
Project description:Microarrays were used to examine gene expression changes that may be present in the fallopian tube epithelium of morphologically normal BRCA1 mutation positive and negative subjects. Fallopian tube epithelia has been implicated as an early point of origin for serous carcninoma. By examining the early events present in the microenvironment of this tissue between BRCA1 mutation carriers and non-carriers, we hoped to elucidate mechanisms that may lead to the development of epithelial ovarian cancer.
2011-04-28 | GSE28044 | GEO
Project description:We generate induced pluripotent stem cells (iPSCs) from healthy individuals and young ovarian cancer patients with germline pathogenic BRCA1 mutations. We then differentiate them into a human iPSC-derived fallopian tube organoid model. We recapitulated BRCA1 mutant ovarian carcinogenesis in vitro and showed tumors in vivo. Using the IPSC derived fallopian tube organoid model, we identify a unique transcriptional profile associated with BRCA1 mutation similar to the ovarian cancer profile.
2022-01-24 | GSE190134 | GEO
Project description:High-grade serous ovarian cancer originates in the fallopian tube and is characterized by ubiquitous mutations in TP53. Here, we generated TP53 single-, TP53/BRCA1 and TP53/MYC double- and TP53/BRCA1/MYC triple-mutant subclones of the fallopian tube-derived cell line FNE1 using CRISPR/Cas9. These mutant subclones were subsequently subjected to RNA sequencing to determine the impact of these oncogenic mutations on signaling pathways.
2021-09-28 | GSE182487 | GEO
Project description:Expression data from non-malignant fallopian tube epithelium
| PRJNA139755 | ENA
Project description:Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis. The purpose of this study was to identify candidate genes possibly involved in pathogenesis of serous ovarian cancer by carrying out a microarray analysis of differentially expressed genes in BRCA1/2- mutation positive ovarian and fallopian tube epithelium derived from RRSO surgery. Freshly frozen ovarian and fallopian tube samples from nine BRCA1/2 mutation carriers scheduled for RRSO were prospectively collected in comparison with five mutation-negative control patients undergoing salpingo-oophorectomy for benign indications. Microarray analysis of genome-wide gene expression was performed on ovarian and fallopian tube samples from BRCA1/2 and control patients. The validation of microarray data was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in selected cases of RRSO samples, and also high grade serous carcinoma samples collected from patients with BRCA phenotype. From 22,733 genes, 454 transcripts were identified that were differentially expressed in BRCA1/2 mutation carriers when statistically compared to controls pooling all ovarian and fallopian tube samples together. Of these, 299 genes were statistically significantly downregulated and 155 genes were upregulated. Differentially expressed genes in BRCA1/2 samples reported here might be involved in serous ovarian carcinogenesis and provide interesting targets for further studies.
2015-02-28 | GSE66387 | GEO
Project description:The purpose of this study was to identify molecular alterations potentially involved in predisposition to adnexal serous carcinoma (SerCa) in the non-malignant fallopian tube epithelium (FTE) of BRCA1/2-mutation carriers, given recent evidence implicating the distal FTE as a common source for SerCa. Keywords: disease state analysis
2008-05-31 | GSE10971 | GEO
Project description:The purpose of this study was to identify molecular alterations potentially involved in predisposition to adnexal serous carcinoma (SerCa) in the non-malignant fallopian tube epithelium (FTE) of BRCA1/2-mutation carriers, given recent evidence implicating the distal FTE as a common source for SerCa. Experiment Overall Design: We obtained and compared gene expression profiles of laser capture microdissected non-malignant distal FTE from 12 known BRCA1/2-mutation carriers (FTEb) and 12 control women (FTEn) during the luteal and follicular phase, as well as 13 high grade tubal and ovarian SerCa.
2008-06-18 | E-GEOD-10971 | biostudies-arrayexpress
Project description:Germline BRCA1 or BRCA2 mutations (mtBRCA1 and mtBRCA2) dramatically increase risk for high-grade serous ovarian cancer (HGSOC), the most commonly diagnosed histotype. Other risk factors for this cancer, which originates primarily in the distal fallopian tube epithelium (FTE), implicate ovulation. To test whether mtBRCA1 or mtBRCA2 FTE cells respond differently to peri-ovulatory follicular fluid (FF) exposure than control patient FTE, gene expression profiles from primary FTE cultures were compared at baseline, 24h after FF exposure, and 24h after FF replacement with culture medium. Hierarchical clustering revealed both FF exposure and BRCA mutation status affect gene expression, with BRCA1 mutation having the greatest impact. Analysis revealed increased NFκB and EGFR signaling at baseline, with increased interferon signaling after recovery from FF exposure in mtBRCA1 samples. Inhibition of EGFR signaling and ISGylation by increased BRCA1 expression was verified in an immortalized FTE cell line, OE-E6/E7, stably transfected with BRCA1. Suppression of ISG15 and ISGylated protein levels by BRCA1 expression was found to be mediated by decreased NFκB signaling and was transiently suppressed by FF exposure. This study demonstrates increased NFκB signaling associated with decreased BRCA1 expression resulting in increased ISG15 and ISGylation following FF exposure, which could represent potential targets for chemoprevention.
2018-05-31 | GSE98699 | GEO