Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Amplicon-Screening of exonic RNA in exon-wide mutant cell libraries of mutant TP53 (Exons 5, 6, 7, 8) in HCT116 cells generated via CRISPR editing

ABSTRACT: To compare the impact of TP53 mutant variants in exon-wide mutant cell libraries, comprehensive mutome libraries of TP53 affecting the Exons 5, 6, 7 and 8 were generated systematically by CRISP/Cas9 editing in HCT116 colorectal carcinoma cells.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Marco Mernberger

PROVIDER: E-MTAB-12861 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Amplicon-Screening of exonic DNA regions in exon-wide mutant cell libraries of mutant TP53 (Exons 5, 6, 7, 8) in HCT116 cells generated via CRISPR editing

Project description:To compare the impact of TP53 mutant variants in exon-wide mutant cell libraries, comprehensive mutome libraries of TP53 affecting the Exons 5, 6, 7 and 8 were generated systematically by CRISP/Cas9 editing in HCT116 colorectal carcinoma cells.

2024-10-16 | E-MTAB-12857 | biostudies-arrayexpress

Amplicon-Screening of genomic DNA regions of mutants in the Exon5 R175 position of TP53 in HCT116 cells generated via CRISPR editing

Project description:To compare the impact of CRISPR-egineered R175 TP53 mutant variants in HCT116 and H460 cells, mutations at the amino acid position 175 were generated systematically by CRISP/Cas9 editing. Here, genomic amplicon regions covering the TP53 Exons 5 were sequenced via targeted sequencing.

2024-10-16 | E-MTAB-14322 | biostudies-arrayexpress

26S proteasome is conserved, therapeutically relevant mediator of mutant p53 gain-of-function in cancer

Project description:Mutant p53 proteins, resulting form frequent TP53 tumor suppressor missense mutations, possess gain-of-function activities and are among the most widespread and robust oncoproteins in human tumors. They are potentially important but understudied therapeutic targets. No studies to date have distinguished common, therapeutically relevant mutant p53 gain-of-function effects, from effects specific to different mutant variants and cell backgrounds. Here we identify 26S proteasome machinery as the common downstream effector controlled by mutant p53s in Triple Negative Breast Cancer (TNBC - aggressive carcinomas with TP53 as the most frequently mutated locus) and conserved in other human cancers. We have identified this pathway using a combination of single-model, multi-method vertical analysis (whole cell proteome, RNA sequencing an ChIP sequencing) and multi-cell line, horizontal analysis of transcriptiomes. We found that different missense mutant p53s regardless of the cell background transcriptionaly activate whole 26S proteasome machinery. Proteasome activity is significantly increased in p53 mutant versus wild-type or knockdown/null status - in cellular and mouse models as well as in human breast tumors. Increased proteasome activity leads to inhibition of tumor suppressive pathways. The control of mutant p53 over proteasome transcription and activity results in the increased resistance to proteasome inhibitors. By combining the mutant p53 targeting agents and proteasome inhibitor we were able to overcome the “bounce-back” proteasome inhibitor resistance mechanism in mutant p53 bearing TNBC cells and xenografts in vivo.

2016-05-03 | PXD001673 | Pride

MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells

Project description:CRISPR screen data

2023-05-31 | E-MTAB-12929 | biostudies-arrayexpress

Targeted sequencing of 49 primary medulloblastoma samples using Illumina TruSight Tumor 15 assay

Project description:The mutation status of TP53 was analyzed by next generation sequencing using the Illumina TruSight Tumor (TST) 15 assay (Illumina) at the Molecular Pathology Center of the Jewish General Hospital (Montreal, QC, Canada). The CAP-compliant clinically validated TST15 assay was performed as per supplier's instruction with 10 ng DNA input. Libraries were sequenced on a MiSeq with a v3 flow cell (Illumina). Data was analyzed with a clinically validated pipeline (NextGene, SoftGenetics) and variants were annotated in Geneticist Assistant (SoftGenetics). The IARC TP53 database version R18 was consulted for the molecular interpretation of TP53 variants (www.p53.iarc.fr).

2018-03-20 | E-MTAB-6546 | biostudies-arrayexpress

Clonal cytogenetics changes in progression of multiple myeloma to extramedullary relapse and plasmocellular leukemia – case report

Project description:Extramedullary relapse (EM) of multiple myeloma (MM) is defined as infiltration of plasma cells (PC) outside of the bone marrow. EM is an aggressive form of the disease with a dismal outcome. We present cytogenetic findings of a 52-year-old female patient who was diagnosed with MM in 2008 and progression of MM to EM and plasmocellular leukemia retrospective analysis of TP53 mutation status showed presence of 2 known missense mutations in exon 6 (c.632C>T) and exon 7 (c.700T>C). EM relapse of this patient was connected to a change of the entire genome profile. We suppose that the extramedullary lesion originated by an expansion of one clone of tumor plasma cells from the bone marrow, which was confirmed by identical genomic profile of both tested samples. Thus, change of ploidy status should be considered as potential hallmark of adverse course of the disease.

2015-10-06 | E-MTAB-3600 | biostudies-arrayexpress

Gene expression profiles of DFCs and SHED 48 hours after in vitro transfection with a TP53 plasmid, a SP1 plasmid, or an empty vector.

Project description:Dental follicle is a loose connective tissue that surrounds the developing tooth. Dental follicle cells (DFCs) have a promising potential for tissue engineering applications including periodontal and bone regeneration. However, little is known about the molecular mechanisms underlying osteogenic differentiation. In a previous study we detected that more than 35 % of genes that are regulated during osteogenic differentiation of DFCs have promoter binding sites for the transcription factors TP53 and SP1. However, the role of these transcription factors in dental stem cells is still unknown. We hypothesize that both factors influence the processes of cell proliferation and differentiation in dental stem cells. Therefore, we transiently transfected DFCs and dental pulp stem cells (SHED; Stem cells from human exfoliated decidiuous teeth) with expression vectors for these transcription factors. After overexpression of SP1 and TP53, SP1 influenced cell proliferation and TP53 osteogenic differentiation in both dental cell types. The effects on cell proliferation and differentiation were less pronounced after siRNA mediated silencing of TP53 and SP1. This indicates that the effects we observed after TP53 and SP1 overexpression are indirect and subject of complex regulation. Interestingly, upregulated biological processes in DFCs after TP53-overexpression resemble the downregulated biological processes in SHED after SP1-overexpression. Here, regulated processes are involved in cell motility, wound healing and programmed cell death. In conclusion, our study demonstrates that SP1 and TP53 influence cell proliferation and differentiation and similar biological processes in both SHED and DFCs. Total RNAs were isolated from dental follicle cells after 48 hours of transfection with a TP53 expressions plasmid, a SP1 expressions plasmid and for control with an empty vector.

2011-08-24 | E-GEOD-31628 | biostudies-arrayexpress

Effect of wtp53-reactivating drug RITA on HCT116 cells

Project description:Since its discovery as a tumour suppressor some fifteen years ago, the transcription factor p53 has attracted paramount attention for its role as “the guardian of the genome”. TP53 mutations occur so frequently in cancer, regardless of patient age or tumour type, that they appear to be part of the life history of at least 50% of human tumours. In most tumours that retain wild-type p53, its function is inactivated due to deregulated HDM2, a protein which binds to p53 and which can inhibit the transcriptional activity of p53 and induce its degradation. RITA is a low-molecular-weight compound which addresses the second group of tumours retaining functionally reactive wt p53. It was found in a screening of the National Cancer Institute (NCI) library of low-molecular-weight compounds based on its ability to selectively kill wtp53-containing cells. RITA binds directly to p53 and diplaces its main destructor Mdm2, as well as inducing a shift in the conformation of p53. This is in contrast to the wtp53-reactivating compound Nutlin3a, which targets Mdm2, inhibiting its ability to degrade p53. Using microarray technology we have explored the effect of RITA on the transcriptome of isogenic cell-lines with knocked-out (KO) or intact (WT) TP53. While the effects on KO cells are below detection limit, the effects on WT cells are profound. The known p53 targets induced are predominately apoptotic, in contrast to the genes affected by Nutlin3a, which are exclusively growth-arrest genes. Keywords: Antitumor agent HCT116 parental and HCT116 p53-null (HCT116 TP53-/-) cells were subjected to treatment with 1uM RITA for 12h, or left untreated. The experiment was done in three independent biological replicates.

2009-02-28 | E-GEOD-11578 | biostudies-arrayexpress

Mouse Synovial Sarcoma Models

Project description:Compare transcriptomes from SS18-SSX1 and SS18-SSX2 tumors 6 tumors analyzed, 3 from each genotype, all initiated by TATCre injection

2016-07-01 | E-GEOD-71843 | biostudies-arrayexpress

RNA and phosphoprotein profiles of TP53- and PTEN-knockouts in MCF10A at baseline and responding to DNA damage

Project description:A wealth of proteogenomic data has been generated using cancer samples to deepen our understanding of the mechanisms of cancer and how biological networks are altered in association with somatic mutation of tumor suppressor genes, such as TP53 and PTEN. To generate functional signatures of TP53 or PTEN loss, we profiled the RNA and phosphoproteomes of the MCF10A epithelial cell line, along with its congenic TP53- or PTEN-knockout derivatives, upon perturbation with the monofunctional DNA alkylating agent methyl methanesulfonate (MMS) vs. mock-treatment. To enable quantitative and reproducible mass spectrometry data generation, the cell lines were SILAC-labeled (stable isotope labeling with amino acids in cell culture), and the experimental design included label swapping and biological replicates. All data are publicly available and may be used to advance our understanding of the TP53 and PTEN tumor suppressor genes and to provide functional signatures for bioinformatic analyses of proteogenomic datasets.

2023-11-20 | PXD028494 | Pride

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