Multiple Malignancy Familial Comparison
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001000333 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Patient (who has had multiple malignancies) has previously been found to harbour a pathogenic p53 variant which is probably mosaic. This finding is based on exome sequencing performed elsewhere. In this study we will resequence the locus in question to ascertain whether the variant is indeed mosaic.
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Project description:Gene expression profiling was determined in BAMC isolated from non-irradiated and irradiated p53-null and p53-WT mice. We selected strongly expressed genes in p53-WT compared to p53-null BAMC. They belonged to different pathways.Also, a number of genes coded secreting proteins that , probably, were responsible for the improved hematopoiesis in p53-null mice.
2018-07-25 | GSE117625 | GEO
Project description:This experiment seeks to ascertain the transcriptional changes in the adult mouse hippocampus (CA1 subregion) that occur following viral knockdown of the histone variant H2A.Z. We are especially interested in understanding the role of this histone variant in memory formation and memory maintenance in the adult central nervous system.
2014-09-09 | GSE58797 | GEO
Project description:Reference standards for mosaic variant detection
| PRJNA758606 | ENA
Project description:Cell competition was originally described in Drosophila as a process for selection of the fittest cells. Using genetic mosaic mouse models and bone marrow chimeras, we have characterized a form of cell competition that selects for the least damaged cells. This competition is controlled by p53 but is distinct from the classical p53-mediated DNA damage response: it persists for months, is specific to the hematopoietic stem and progenitor cells, and depends on the relative rather than absolute level of p53 in competing cells. The competition appears to be mediated by a non-cell autonomous induction of growth arrest and senescence-related gene expression in outcompeted cells with higher p53 activity. p53-mediated cell competition of this type could potentially contribute to the clonal expansion of incipient cancer cells. This microarray experiment is aimed at identification of candidate genes that mediate this competition. It compares mRNA expression patterns of HSCs with different levels of p53 activity in either competitive or non-competitive conditions (isolated from either wild type, mutant p53, or mosaic wt/mutant p53 mice (R26-mp53mice) after irradiation).
2010-04-01 | GSE20912 | GEO
Project description:Reversible p53 activation using a temperature variant of p53
2012-04-30 | E-MEXP-3224 | biostudies-arrayexpress
Project description:Oncogene-induced senescence (OIS) is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We identified BRD7, a bromodomain-containing protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. Intriguingly, in human breast tumours harbouring wild-type, but not mutant p53, the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300, and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation, and promoter activity. Thus, BRD7 suppresses tumourigenicity by serving as a p53 cofactor required for efficient induction of p53-dependent OIS.
2010-03-14 | GSE20076 | GEO
Project description:We have developed cdk4/hTERT-immortalized normal human bronchial epithelial cells (HBECs) to study lung cancer pathogenesis. By studying the oncogenic effect of common lung cancer alterations (p53, KRAS, and c-MYC) we demonstrate the ability of this model to characterize the stepwise transformation of bronchial epithelial cells to full malignancy. Using HBECs derived from multiple individuals we found: 1) the combination of five genetic alterations (p53, KRASV12, c-MYC, CDK4 and hTERT) is sufficient for full tumorigenic conversion of HBECs; 2) high levels of KRASV12 are required for full malignant transformation of HBECs, however these levels also stimulate oncogene-induced senescence; 3) RAS-induced senescence is largely bypassed with loss of p53 function; 4) over-expression of c-MYC greatly enhances malignancy but only in the context of sh-p53+KRASV12; 5) HBECs from different individuals vary in their sensitivity to transformation by these oncogenic manipulations; 6) serum-induced epithelial-to-mesenchymal transition (EMT) increases in vivo tumorigenicity; 7) genetically-identical clones of transformed HBECs exhibit pronounced differences in tumor growth, histology, and differentiation as well as sensitivity to standard platinum-based chemotherapies; and 8) an mRNA signature derived from tumorigenic and non-tumorigenic clones is predictive of outcome in lung cancer patients. Collectively, we demonstrate this HBEC model system can be used to study the effect of oncogenic mutations on malignant progression, oncogene-induced senescence, and EMT along with clinically translatable applications such as development of prognostic signatures and drug response phenotypes. Human bronchial epithelial cells (HBECs) immortalized with cdk4 and hTERT were transformed with p53 knockdown, KrasV12 and cMYC over-expression and profiled on Illumina HumanHT-12 V4.0 expression beadchips. Transformed HBECs were grown in two different growth media: KSFM (defined, serum-free medium) or R10 (RPMI with 10% FBS) as indicated. Clones were isolated from HBECs with sh-p53 + KrasV12 and sh-p53 + KrasV12 + cMYC.
2013-07-01 | E-GEOD-40828 | biostudies-arrayexpress
Project description:The tumor suppressor protein p53 is a transcription factor that is referred to as the “guardian of the genome” and plays an important role in cancer development. P53 is active as a tetramer; the S100β homodimer binds to the intrinsically disordered C-terminus of p53, affecting its transcriptional activity. The p53/S100β complex is regarded as highly promising therapeutic target in cancer. It has been suggested that S100β exerts its oncogenic effects by altering the p53 oligomeric state. Our aim was to study the structures and oligomerization behavior of different p53/S100β complexes by electrospray ionization mass spectrometry (ESI-MS), cross-linking mass spectrometry (XL-MS), and surface plasmon resonance (SPR). For this, wild-type p53 and single amino acid variants, representing different oligomeric states of p53 (tetrameric wild-type, dimeric L344A variant, and monomeric L344P variant) were individually investigated regarding their binding behavior towards S100β. The stoichiometry of the different p53/S100β complexes were determined by ESI-MS showing that tetrameric, dimeric, and monomeric p53 variants all bind to an S100β dimer. In addition, XL-MS revealed the topologies of the p53/S100β complexes to be independent of p53’s oligomeric state. With SPR, the thermodynamic parameters were determined for S100β binding to tetrameric, dimeric or monomeric p53 variants. Our data prove that the S100β homodimer binds to different oligomeric states of p53 with identical stoichiometries and similar binding affinities. This emphasizes the need for alternative explanations to describe the molecular mechanisms underlying p53/S100β interaction.
2022-10-14 | PXD029914 | Pride
Project description:Oncogene-induced senescence (OIS) is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We identified BRD7, a bromodomain-containing protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. Intriguingly, in human breast tumours harbouring wild-type, but not mutant p53, the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300, and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation, and promoter activity. Thus, BRD7 suppresses tumourigenicity by serving as a p53 cofactor required for efficient induction of p53-dependent OIS. We recorded mRNA expression profiles of BJ primary fibroblasts expressing the oncogene RasV12 and either control vector, one of two BRD7 knockdown vectors, or p53 knockdown vector. In addition, we profiled genome-wide protein DNA interactions for p53 and BRD7 using ChIP-Seq. p53- and BRD7-binding sites were recorded in RasV12-expressing BJ cells; as a control we used knockdown of the gene of interest (BRD7 or p53).
2010-03-14 | E-GEOD-20076 | biostudies-arrayexpress