Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA191588 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identification of Targetable FGFR Gene Fusions in Diverse Cancers
| PRJNA191587 | ENA
Project description:<p>In this study, patients with advanced cancer across all histologies were enrolled in our IRB approved clinical sequencing program, called MI-ONCOSEQ, to go through an integrative sequencing which includes whole exome sequencing of the tumor and matched normal, and transcriptome sequencing. Four index cases were identified which harbor gene rearrangements of FGFR2 including two cholangiocarcinoma cases, a metastatic breast cancer case, and a metastatic prostate cancer case. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, including TCGA, we identified FGFR gene fusions with intact kinase domains of FGFR1, FGFR2, or FGFR3 in cholangiocarcinoma, breast cancer, prostate cancer, lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins in vitro induced cell proliferation, and bladder cancer cell lines that harbors FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Due to the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts which incorporate transcriptome analysis for gene fusions are poised to identify rare, targetable FGFR fusions across diverse cancer types.</p>
| phs000602 | dbGaP
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:By combining extensive biochemical fractionation with quantitative mass spectrometry, we directly examined the composition of soluble multiprotein complexes among diverse animal models. The project has been jointly supervised by Andrew Emili and Edward M. Marcotte. Project website: http://metazoa.med.utoronto.ca
2015-07-22 | PXD002322 | Pride
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:We first verified that erdafitinib is synergistic with quisinostat in vitro and confirmed that the combinational treatment can significantly enhance the inhibition of tumor growth and prolong the survival in vivo for bladder cancers with FGFR3 fusions. Next, in order to understand the underlying molecular mechanisms of this synergy, we performed RNA-seq analysis. We revealed that quisinostat can concomitantly inhibit FGFR signaling with erdafitinib by suppressing the translation of FGFR3 fusions. In addition, quisinostat can also sensitize bladder cancer cells to erdafitinib by downregulating HDGF, which is a second mechanism of the synergy independent of FGFR signaling.
2022-10-11 | GSE214814 | GEO
Project description:<p>In this study, patients with advanced cancer across all histologies were enrolled in our IRB approved clinical sequencing program, called MI-ONCOSEQ, to go through an integrative sequencing which includes whole exome sequencing of the tumor and matched normal, and transcriptome sequencing. Four index cases were identified which harbor gene rearrangements of FGFR2 including two cholangiocarcinoma cases, a metastatic breast cancer case, and a metastatic prostate cancer case. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, including TCGA, we identified FGFR gene fusions with intact kinase domains of FGFR1, FGFR2, or FGFR3 in cholangiocarcinoma, breast cancer, prostate cancer, lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins in vitro induced cell proliferation, and bladder cancer cell lines that harbors FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Due to the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts which incorporate transcriptome analysis for gene fusions are poised to identify rare, targetable FGFR fusions across diverse cancer types.</p>
| phs000602.v1.p1 | EGA
Project description:A subset of triple negative breast cancers (TNBC) are characterized by genetic alterations in fibroblast growth factor receptors (FGFR) including amplifications, activating mutations or gene fusions. However, despite this genetic evidence of FGFR-dependency, FGFR inhibitors have shown only limited clinical efficacy in TNBC, suggesting the presence of intrinsic or adaptive resistance mechanisms. Using genome-wide CRISPR screens, we found that resistance to FGFR inhibition is mediated by activation of the mTORC1 and YAP pathways. Prolonged FGFR inhibition increased expression of several amino acid transporters resulting in increased cellular level of certain amino acids and activation of the mTORC1 amino acid sensing pathway. Epigenomic analyses revealed that FGFR inhibition reorganized YAP/TEAD associated enhancers leading to the upregulation of YAP target genes including the amino acid transporters upstream of mTORC1. Remarkably, mTORC1 and FGFR inhibitors synergistically blocked the growth of TNBC cells in vitro and in patient-derived xenografts. These findings define a novel epigenetic feedback mechanism involving intracellular amino acid levels leading to targeted therapy resistance in TNBC, and offers a combinatorial drug treatment strategy to improve clinical outcomes for this aggressive breast cancer subtype.
2021-09-09 | GSE168026 | GEO
Project description:A subset of triple negative breast cancers (TNBC) are characterized by genetic alterations in fibroblast growth factor receptors (FGFR) including amplifications, activating mutations or gene fusions. However, despite this genetic evidence of FGFR-dependency, FGFR inhibitors have shown only limited clinical efficacy in TNBC, suggesting the presence of intrinsic or adaptive resistance mechanisms. Using genome-wide CRISPR screens, we found that resistance to FGFR inhibition is mediated by activation of the mTORC1 and YAP pathways. Prolonged FGFR inhibition increased expression of several amino acid transporters resulting in increased cellular level of certain amino acids and activation of the mTORC1 amino acid sensing pathway. Epigenomic analyses revealed that FGFR inhibition reorganized YAP/TEAD associated enhancers leading to the upregulation of YAP target genes including the amino acid transporters upstream of mTORC1. Remarkably, mTORC1 and FGFR inhibitors synergistically blocked the growth of TNBC cells in vitro and in patient-derived xenografts. These findings define a novel epigenetic feedback mechanism involving intracellular amino acid levels leading to targeted therapy resistance in TNBC, and offers a combinatorial drug treatment strategy to improve clinical outcomes for this aggressive breast cancer subtype.
2021-09-09 | GSE168024 | GEO