Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA257428 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 – SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors. 53 Wilms tumor samples were selected for RNA extraction and hybridization on Affymetrix Affymetrix Human Genome U133 Plus 2.0 Arrays.
2015-02-18 | E-GEOD-53224 | biostudies-arrayexpress
Project description:Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 – SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors.
2015-02-18 | GSE53224 | GEO
Project description:Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find novel therapeutic leads for this subgroup of patients, we analyzed 58 blastemal-type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large independent replication cohort. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA expression patterns in tumors, which was functionally validated in cell lines transfected with mutant DROSHA. total samples analyzed are 16, each done as technical replicate
2015-02-18 | E-GEOD-60081 | biostudies-arrayexpress
Project description:Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find novel therapeutic leads for this subgroup of patients, we analyzed 58 blastemal-type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large independent replication cohort. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA expression patterns in tumors, which was functionally validated in cell lines transfected with mutant DROSHA.
2015-02-18 | GSE60081 | GEO
Project description:Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. In order to find novel therapeutic leads for this subgroup of patients, we analyzed 58 such Wilms tumors by exome and transcriptome analysis and validated our findings in larger independent cohorts. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA profiles in tumors, which we confirmed in cell lines transfected with mutant DROSHA.
| EGAS00001000906 | EGA
Project description:Through whole-exome sequencing we identified somatic missense mutations in DICER1 and DROSHA in Wilms tumor, a childhood kidney cancer. DICER1 and DROSHA are key enzymes in the microRNA biogenesis pathway. To determine the effect of these mutations on microRNA expression, we prepared small RNAs from Wilms tumors and used next-generation sequencing to determine the expression levels of microRNAs in the tumors. Comparison of miRNA expression in tumors with and without mutations in DICER1 or DROSHA.
2015-04-21 | E-GEOD-56955 | biostudies-arrayexpress
Project description:Through whole-exome sequencing we identified somatic missense mutations in DICER1 and DROSHA in Wilms tumor, a childhood kidney cancer. DICER1 and DROSHA are key enzymes in the microRNA biogenesis pathway. To determine the effect of these mutations on microRNA expression, we prepared small RNAs from Wilms tumors and used next-generation sequencing to determine the expression levels of microRNAs in the tumors.
2015-04-21 | GSE56955 | GEO
Project description:We addressed the requirement of DGCR8, DROSHA and DICER functions in developing and adult Schwann cells (SCs) using mouse mutants. We found that the microprocessor components DGCR8 and DROSHA are crucial for axonal radial sorting and to establish correct SC numbers upon myelination. Transcriptome analysis revealed that the microprocessor is essential to prevent aberrant accumulation and de novo expression of injury-response genes. Those genes are predicted targets of stage-specifically enriched miRNAs. In agreement, DGCR8 and DICER are required for proper maintenance of the myelinated SC state. We conclude that the miRNA pathway is crucial for preventing inappropriate activity of injury response genes in developing and adult SCs.
2018-10-08 | GSE109075 | GEO
Project description:The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 contains two double-stranded RNA binding motifs that recognize the RNA substrate, whereas Drosha functions as the endonuclease. We have used high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify endogenous RNA targets of DGCR8 in mammalian cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs comprised several hundred mRNAs as well as snoRNAs and long non-coding RNAs. We found that DGCR8 together with Drosha controls the abundance of several mRNAs, as well as long non-coding RNAs, such as MALAT-1. By contrast, the DGCR8-mediated cleavage of snoRNAs is independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Interestingly, binding of DGCR8 to cassette exons, acts as a novel mechanism to regulate the relative abundance of alternatively spliced isoforms. Collectively, these data provide new insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs. Comparison of RNAs associated to both endogenous (D8) and overexpressed (T7) DGCR8 in HEK293T cells
2012-07-15 | E-GEOD-39086 | biostudies-arrayexpress
Project description:The Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 contains two double-stranded RNA binding motifs that recognize the RNA substrate, whereas Drosha functions as the endonuclease. We have used high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify endogenous RNA targets of DGCR8 in mammalian cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs comprised several hundred mRNAs as well as snoRNAs and long non-coding RNAs. We found that DGCR8 together with Drosha controls the abundance of several mRNAs, as well as long non-coding RNAs, such as MALAT-1. By contrast, the DGCR8-mediated cleavage of snoRNAs is independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Interestingly, binding of DGCR8 to cassette exons, acts as a novel mechanism to regulate the relative abundance of alternatively spliced isoforms. Collectively, these data provide new insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs.
2012-07-15 | GSE39086 | GEO