Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EGAS00001000310-sc-20160629 - samples

ABSTRACT: The disordered transcriptomes of cancer encompass direct effects of somatic mutation on transcription; co-ordinated secondary alterations in transcriptional pathways; and increased transcriptional noise. To catalogue the rules governing how somatic mutation Overall, 59% of 6980 exonic substitutions were expressed. Compared to other classes, nonsense mutations showed lower expression levels than expected with patterns characteristic of nonsense-mediated decay. 14% of 4234 genomic rearrangements caused transcriptional abnormalities, including exon skips, exon reusage, fusion transcripts and premature poly-adenylation. We found productive, stable transcription from sense-to-antisense gene fusions and gene-to-intergenic rearrangements, suggesting that these mutation classes may drive more transcriptional disruption than previously suspected. Systematic integration of transcriptome with genome data therefore reveals the rules by which transcriptional machinery interprets somatic mutation.

PROVIDER: EGAD00001002236 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

EGAS00001000195-5-sc-20160630 - samples

Project description:The disordered transcriptomes of cancerÃ‚Â encompass direct effects of somatic mutation on transcription; co-ordinatedÃ‚Â secondary alterations in transcriptional pathways; and increasedÃ‚Â transcriptional noise. To catalogue the rules governing how somatic mutationÃ‚Â Overall, 59% of 6980 exonicÃ‚Â substitutions wereÃ‚Â expressed. Compared to other classes, nonsense mutations showed lowerÃ‚Â expression levels than expected withÃ‚Â patterns characteristic ofÃ‚Â nonsense-mediated decay. 14% of 4234 genomic rearrangements causedÃ‚Â transcriptional abnormalities,Ã‚Â including exon skips, exon reusage, fusionÃ‚Â transcripts and premature poly-adenylation. We found productive, stableÃ‚Â transcriptionÃ‚Â from sense-to-antisense gene fusions and gene-to-intergenicÃ‚Â rearrangements, suggesting that these mutation classes may drive moreÃ‚Â transcriptional disruption than previously suspected. Systematic integration ofÃ‚Â transcriptome with genome data therefore reveals theÃ‚Â rules by whichÃ‚Â transcriptional machinery interprets somatic mutation.

| EGAD00001002237 | EGA

Phosphoproteomics of truncated FGFR2, a clinically actionable oncogene in multiple cancers

Project description:Somatic hotspot mutations and structural amplifications and fusions affecting fibroblast growth factor receptor 2 (FGFR2) occur in multiple cancer types. However, clinical responses to FGFR inhibitors (FGFRi) have remained variable, emphasizing a need to better understand which FGFR2 alterations are oncogenic and targetable. Here we applied transposon-based screening and tumor modelling in mice to uncover truncation of exon (E) 18 of Fgfr2 as a potent driver mutation. Human oncogenomic datasets revealed a diverse set of FGFR2 alterations, including rearrangements (REs), E1-E17 partial amplifications, and E18 nonsense and frameshift mutations, each causing transcription of E18-truncated FGFR2 (FGFR2deltaE18). Somatic modelling in mice and human tumor cell lines using a compendium of FGFR2deltaE18 and full-length variants identified FGFR2deltaE18-truncation as potent single-driver alteration in cancer. Here we show the phosphoproteomic landscape of FGFR2 variants in murine epithelial cell (MEC) lines and mouse tumors. Global (STY) phosphoproteomics using IMAC and phosphotyrosine phosphoproteomics using pTyr IP’s are combined with DIA protein expression data to uncover oncogenic signaling of clinically-relevant FGFR2 variants.

2022-06-06 | PXD031711 | Pride

Exploration and clinical validation of molecular typing of early colorectal cancer

Project description:Interventions: Case series:None Primary outcome(s): exon genes;transcriptional expression;proteome;protein phosphorylation group Study Design: Sequential

| 2739647 | ecrin-mdr-crc

Co-transcriptional splicing regulates 3' end cleavage during mammalian erythropoiesis

Project description:Pre-mRNA processing steps are tightly coordinated with transcription in many organisms. To determine how co-transcriptional splicing is integrated with transcription elongation and 3' end formation in mammalian cells, we performed long read sequencing of individual nascent RNAs and PRO-seq during mouse erythropoiesis. Splicing was not accompanied by transcriptional pausing and was detected when RNA polymerase II (Pol II) was within 75-300 nucleotides of 3' splice sites (3'SSs), often during transcription of the downstream exon. Interestingly, several hundred introns displayed abundant splicing intermediates, suggesting that splicing delays take place between the two catalytic steps. We also observed gene-specific differences in co-transcriptional splicing efficiency, and intron retention correlated with inefficient 3' end cleavage. Remarkably, a thalassemia patient-derived mutation introducing a cryptic 3'SS improves both splicing and 3' end cleavage of individual beta-globin transcripts, revealing that functional coupling between the two co-transcriptional processes is a determinant of productive gene output.

2021-01-12 | GSE144205 | GEO

Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic-RNA-Seq

Project description:Somatic mutations of RUNX1, which encodes the myeloid and lymphoid transcriptional factor RUNX1, are common in both B- and T- acute lymphoid leukemia (ALL) and are associated with poor prognosis of T-ALL. However, there has been no comprehensive investigation of the pattern or prevalence of RUNX1 germline mutation in both B- and T-ALL. Here we report germline RUNX1 variants in 1.23% of B-ALL and 2.11% of T-ALL, identifying 31 unique variants in 62 B-ALL and 18 unique variants in 26 T-ALL children. The majority of frameshift and nonsense variants affected RUNX1 function in transcriptional regulation, hematopoiesis, and cellular proliferation. We identified JAK3 as the most frequent somatic mutation in T-ALL with RUNX1 variants. These results not only identify RUNX1 as a leukemia predisposition gene but also further underline the importance of germline genetic variants to the development of ALL

2021-12-31 | GSE178237 | GEO

Germline RUNX1 Variation and Predisposition to Childhood Acute Lymphoblastic-ChIP-Seq

2021-12-31 | GSE178238 | GEO

chromothripsis in neuroblastoma

Project description:RNA-seq for four neuroblastoma samples (Paired-end protocol). Neuroblastoma is a pediatric cancer of the peripheral nervous system in which structural chromosome aberrations are emblematic of aggressive tumors. In this study, we investigated somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries (SRA accession number ERP001414) and RNA-seq. In one cell line and in the two primary tumors, this approach confirmed the localization of the majority of rearrangements within one or two chromosomes, consistent with the phenomenon of chromothripsis. RNA-seq experiments confirmed expression of several predicted chimeric genes and genes with disrupted exon structure including ALK, NBAS, FHIT, PTPRD and ODZ4. RNA-seq analysis allowed the identification of abnormal transcripts expressed from genomic rearrangements that may be involved in neuroblastoma oncogenesis.

2013-03-03 | E-MTAB-1367 | biostudies-arrayexpress

RNA-seq analysis of Scn1a +/- mouse

Project description:In this study we recapitulated in the mouse, an SCN1A mutation found in a human Dravet syndrome (DS) patient. The targeted mutation, NC_000068.7:g.66293870C>G (GRCm38.p6) lies in a highly conserved alternate poison exon (20N) of the mouse Scn1a. We performed molecular and behavioral analysis of Scn1a +/- mice and Scn1a +/+ littermate controls. We found that the mutation causes Scn1a mRNA and protein levels to be reduced by about 50% in brain compared to control mice. In addition, the Scn1a +/- mice exhibit behavioral phenotypes seen in previous DS model mice models. We performed qPCR and RNA-seq analysis of the brains of four Scn1a +/- mice and four Scn1a +/+ littermate controls. There was a ~50% reduction in Scn1a RNA-seq counts in Scn1a +/- mice. Our data provides evidence that the mutation causes increased inclusion of the poison exon 20N in Scn1a transcripts leading to nonsense mediated decay and reduction in protein levels.

2020-08-01 | GSE153461 | GEO

FIR inhibition in HCC cells (Hep3B)

Project description:siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA Together with far upstream element binding protein (FBP), the FBP-interacting repressor (FIR) represents a molecular tool for the transcriptional fine tune regulation of target genes. Previous evidence indicates that strong overexpression of FBP in human hepatocellular carcinoma (HCC) supports tumor growth and correlates with poor patient prognosis. However, the role of the transcriptional repressor FIR in hepatocarcinogenesis remains poorly delineated. We show that overexpression of FIR correlates with tumor dedifferentiation and tumor cell proliferation in about 60% of primary HCCs. Elevated FIR levels are associated with genomic gains of the fir gene locus at chromosome 8q24.3 in human HCC specimens. In vitro, nuclear enrichment of FIR supports HCC cell proliferation and migration. Expression profiling of HCC cells after siRNA-mediated silencing of FIR identified the transcription factor DP-1 (TFDP1) as a transcriptional target of FIR. Surprisingly, FIR stimulates the expression of FBP in a TFDP1/E2F-dependent manner. FIR splice variants lacking or containing exon 2 and/or exon 5 are expressed in the majority of HCCs. Specific inhibition of FIR isoforms with and without exon 2 revealed that all FIR splice variants facilitate tumor-supporting effects. This finding was confirmed in xenograft transplantation experiments with lentiviral-infected shRNA targeting all FIR variants as well as FIR with and without exon 2. In summary, high-level nuclear FIR does not facilitate repressor properties but supports tumor growth in HCC cells. Thus, the pharmacological inhibition of FIR might represent a promising therapeutic strategy for HCC patients. Expression profiling of cells transfected with scrambled/nonsense siRNA (control), and after siRNA-mediated FIR inhibition.

2014-09-03 | E-GEOD-55692 | biostudies-arrayexpress

ALASCCA-A randomized double-blind placebo-controlled study with ASA treatment in colorectal cancer patients with mutations in the PI3K signaling pathway

Project description:Primary objectives: To determine whether adjuvant treatment with 160 mg ASA once daily for 3 years can improve Time To Recurrence (TTR) in patients with colorectal cancer with somatic alterations in the PIK3CA (exon 9 and 20) compared with placebo. Primary endpoints: Time To Recurrence (TTR) at 3 years in patients with tumors harboring PIK3CA mutations in exon 9 and 20.

| 2534988 | ecrin-mdr-crc

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data