Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA353154 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genetic Basis of Breast Cancer Resistance in BRCA1+ Carrier
| PRJNA353153 | ENA
Project description:Microarrays were used to determine relative global gene expression changes in WT and BRCA1-mutation carrier breast epithelium as well as tumors created from WT and BRCA1-mutation carrier breast epithelial cells.
2011-02-04 | GSE25835 | GEO
Project description:Microarrays were used to determine relative global gene expression changes in WT and BRCA1-mutation carrier breast epithelium as well as tumors created from WT and BRCA1-mutation carrier breast epithelial cells. Total RNA was isolated from freshly dissociated mammary epithelilal cells obtained from disease-free prophylactic masectomy tissues of 4 different BRCA1-mutation carriers or 4 different reduction mammoplasty tissues from non-mutation carriers. Total RNA was also isolated from fresh tumor tissues derived from in vivo transformed human mammary epithelial cells created from cells obtained from WT or BRCA1-muation carrires. Dissociated mammary epithelial cells were transduced with lentiviruses encoding mutant p53, mutant ras, mutant PI3K and cyclin D1 and injected into in humanized glands. There were four tumor tissues isolated for each genetic background.
2011-02-04 | E-GEOD-25835 | biostudies-arrayexpress
Project description:Breast cancer is the most common cancer in females, affecting one in every eight women and accounting for the majority of cancer-related deaths in women worldwide. Germline mutations in the BRCA1 and BRCA2 genes are significant risk factors for specific subtypes of breast cancer. BRCA1 mutations are associated with basal-like breast cancers, whereas BRCA2 mutations are associated with luminal-like disease. Defects in mammary epithelial cell differentiation have been previously recognized in germline BRCA1/2 mutation carriers even before cancer incidence. However, the underlying mechanism is largely unknown. Here, we employ spatial transcriptomics to investigate defects in mammary epithelial cell differentiation accompanied by distinct microenvironmental alterations in preneoplastic breast tissues from BRCA1/2 mutation carriers and normal breast tissues from non-carrier controls. We uncovered spatially defined receptor-ligand interactions in these tissues for the investigation of autocrine and paracrine signaling. We discovered that β1-integrin-mediated autocrine signaling in BRCA2-deficient mammary epithelial cells may differ from BRCA1-deficient mammary epithelial cells. In addition, we found that the epithelial-to-stromal paracrine signaling in the breast tissues of BRCA1/2 mutation carriers is greater than in control tissues. More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than non-carrier breast tissues with more integrin receptor-expressing stromal cells. Implications: These results suggest alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.
2023-10-11 | GSE234017 | GEO
Project description:While new defects in BRCA1 are still being found, it is unclear whether current breast cancer diagnostics misses many BRCA1-associated cases. A reliable test that is able to indicate the involvement of BRCA1 deficiency in cancer genesis could support decision making in genetic counselling and clinical management. To find BRCA1-specific markers and explore the effectiveness of the current diagnostic strategy, we designed a classification method, validated it and examined whether we could find BRCA1-like breast tumours in a group of patients initially diagnosed as non-BRCA1/2 mutation carriers. A classifier was built based on array-CGH profiles of 18 BRCA1-related and 32 control breast tumours, and validated on independent sets of 16 BRCA1-related and 16 control breast carcinomas. Subsequently, we applied the classifier to 48 breast tumours of patients from Hereditary Breast and Ovarian Cancer (HBOC) families in whom no germ line BRCA1/BRCA2 mutations were identified. The classifier showed an accuracy of 91% when applied to the validation sets. In 48 non-BRCA1/2 patients, only two breast tumours presented a BRCA1-like CGH profile. Additional evidence for BRCA1 dysfunction was found in one of these tumours. We here describe the specific chromosomal aberrations in BRCA1-related breast carcinomas. We developed a predictive genetic test for BRCA1-association and show that BRCA1-related tumours can still be identified in HBOC families after routine DNA diagnostics.
2010-12-02 | GSE9021 | GEO
Project description:Identifying germline BRCA1/2 mutation carriers is vital for reducing their risk of breast and ovarian cancer; however, many carriers are not referred for genetic testing. While population-wide testing is not feasible, a cheap functional screen for phenotypic ‘BRCAness’ could guide efforts for focused genetic counseling and improve cancer prevention and early detection. The aim of this study was to derive a serum-based miRNA panel to identify BRCA1/2 mutation carriers among healthy controls. We performed a diagnostic biomarker study based on serum samples collected between by six international cohorts. Serum samples from 653 healthy women with known mutation status of BRCA1 and BRCA2 were used in the analysis. All individuals had no history of prior cancer or any detected malignancies for at least 12 months after sample collection. Among the study population, 350 (53.6%) subjects had BRCA mutations and 303 (46.4%) were BRCA1/2 – wild-type. In all individuals, we isolated and quantified miRNAs expression using RNA-sequencing. Variable selection based on differential expression analysis on merged, batch adjusted cohorts was performed to identify a set of miRNAs associated with BRCA mutation carrier status.
2023-05-02 | GSE226445 | GEO
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. Comparison of the genome wide profiles of the BRCA protein complex (BRCA1 and PALB2) and phosphorylated RNAPII (P-Ser2) in MCF10A cells by ChIP-seq. Effect of BRCA1 and PALB2 knockdown (shRNAs) on transcription was assessed by RNA-seq.
2013-09-30 | E-GEOD-40591 | biostudies-arrayexpress
Project description:PARP inhibitor and platinum based drugs such as cisplatin are promising therapies for triple negative breast cancer and exploit the deficiencies in BRCA1 or BRCA2, or homologous recombination repair defects. However, PARP inhibitor resistance is proven to be a major clinical problem. Acquired PARP inhibitor resistance has been linked with co-resistance to platinum-based drugs. To determine how acquired olaparib resistance affects cisplatin response and whether this is influenced by their BRCA1 status, we performed RNAseq transcriptome analysis of isogenic triple negative breast cancer models of olaparib resistance with normal and mutant BRCA1.
2021-07-22 | GSE165914 | GEO
Project description:<p>Our study addressed a specific question in NCI RFA-CA-12-022: "What underlying causal events - e.g., genetic, epigenetic, biologic, behavioral, or environmental - allow certain individuals to survive beyond the expected limits of otherwise highly lethal cancers?". A germline mutation in BRCA1 (BRCA1+) is the most penetrant genetic predisposition for breast cancer. Nevertheless, a portion of BRCA1+ carriers does not develop breast cancer in their lifetime, suggesting that the genetic predisposition can be antagonized by resistant factors. BRCA1+ was inherited from an ancestor of the carrier family thousand years ago. We hypothesize that evolution could select certain genetic components to suppress oncogenesis caused by the predisposition. We compared germline variants in all genes in 27 pairs of breast cancer-unaffected and -affected BRCA1+ carriers, each pair inherited the same BRCA1+. We identified 12 deleterious variants enriched in breast cancer-unaffected carriers, all are common variants. A variant rs3735400 is located in ANLN, a cytokinesis-essential gene. Overexpression of variant-containing ANLN and suppressed expression of endogenous ANLN decrease ANLN nuclear localization and delay cell growth. Our findings suggest that common variants can be selected to resist oncogenesis imposed by BRCA1+.</p>
| phs001243 | dbGaP