Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: phs000491.v1.p1
PROVIDER: PRJNA157021 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. The RNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal kidney cortices were labeled and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays.
2012-06-09 | E-GEOD-36895 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice retained >92% of mutations and exhibited similar DNA copy number alterations to corresponding primary tumors. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. The genomic DNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal samples were labeled and hybridized to Affymetrix SNP arrays 6.0.
2012-06-09 | E-GEOD-25540 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.
2012-06-10 | GSE36895 | GEO
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice retained >92% of mutations and exhibited similar DNA copy number alterations to corresponding primary tumors. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.
2012-06-10 | GSE25540 | GEO
Project description:BRCA1-associated protein 1 (BAP1) is a member of the ubiquitin C‑terminal hydrolase family of deubiquitinating enzymes and is implicated in transcriptional regulation. The BAP1 gene is mutated in about 10% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, suggesting that BAP1 may be a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing WT BAP1 is unclear. Here, we assessed the expression and function of BAP1 using human ccRCC specimens and cell lines.
2019-04-18 | PXD012288 | Pride
Project description:PBRM1 is a component of the PBAF chromatin remodelling complex and has been observed to be deregulated in a significant proportion of patients with clear-cell Renal Cell Carcinoma (ccRCC). This study employs RNA-Seq to identify differentially expressed genes in cellular models of ccRCC by expressing PBRM1 in PBRM1-deficient Caki2 cells.
2016-05-04 | GSE76199 | GEO
Project description:DNA Copy-Number Alterations in clear-cell Renal Cell Carcinoma (ccRCC) Tumors and Tumorgrafts for samples deficient in BAP1 or PBRM1
| PRJNA134015 | ENA
Project description:The proteome of clinical tissue samples diagnosed with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were evaluated analyzed along with the dataset identifier PXD022018 to establish a potential discriminative biomarker panel of proteins for these tumors subtypes.
2021-12-15 | PXD023296 | Pride
Project description:We identified ADIRF-AS1 as a BMAL1-CLOCK regulated circadian lncRNA. Loss of ADIRF-AS1 in U2OS cells altered rhythmicity of clock-controlled genes and expression of genes associated with cell adhesion and the extracellular matrix (ECM) but did not affect neighboring genes in cis. Affinity based enrichment of U2OS ADIRF-AS1-interacting proteins identified all components of the tumor suppressive PBAF (PBRM1/BRG1) complex. Because PBRM1 is a tumor suppressor mutated in 40% of clear cell renal carcinoma (ccRCC) cases, we studied ccRCC 786O cells and also found PBRM1 bound to ADIRF-AS1. Reducing ADIRF-AS1 expression in 786O and A498 ccRCC cells decreased expression of PBAF-suppressed genes, consistent with ADIRF-AS1 acting to antagonize the function of PBAF. Loss of PBRM1, however, rescued PBAF responsive cell cycle genes in ADIRF-AS1 KO 786O ccRCC cells. Importantly, ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant PBRM1 tumors. In this regard, loss of ADIRF-AS1 did not affect in vitro 786O cell growth, but strikingly eliminated in vivo tumorigenesis, which was partially rescued by concurrent loss of PBRM1. This rescue, however, requires Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1 in regulating the ECM. Collectively, our findings suggest that ADIRF-AS1 functions partly to antagonize the tumor suppressive effect of the PBAF complex and behaves as an unforeseen BMAL1-regulated, oncogenic lncRNA.
| MSV000090286 | MassIVE
Project description:PBRM1 is lost in 40% of clear cell renal cell carcinomas (ccRCC) and the combined loss of VHL and PBRM1 drives ccRCC tumorigenesis. PBRM1 is an accessory subunit of the PBAF subclass of the SWI/SNF chromatin remodeler and despite its well-established role as a tumor suppressor, we have limited understanding of how PBRM1 regulates the chromatin. Now we report that PBRM1 binds to promoter-proxy regions with footprints at +1 to + 3 nucleosomes. PBRM1-deficient PBAF complexes lose BRD7 but retain ARID2, while tethered to SMARCA4. The lack of PBRM1-BRD7 module compromises the targeting specificity of the PBAF complexes, causes their genomic redistribution and impairs the repressive ability of PBAF complexes. Subsequently, PBRM1-deficient PBAF complexes prime the chromatin at de novo sites for transcriptional activation of pro-survival genes involved in hypoxia and cholesterol synthesis. Therefore, PBRM1 safeguards the chromatin by repressing aberrant liberation of pro-survival genes by residual PBRM1-deficient SWI/SNF complexes.
2021-07-24 | PXD020554 | JPOST Repository