Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary KIT Mutations

ABSTRACT: Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary KIT Mutations

PROVIDER: PRJNA1036559 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26700351_1.fastq.gz	Fastqsanger.gz
	SRR26700351_2.fastq.gz	Fastqsanger.gz
	SRR26700352_1.fastq.gz	Fastqsanger.gz
	SRR26700352_2.fastq.gz	Fastqsanger.gz
	SRR26700353_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

Unraveling the Mechanisms of Sensitivity to Anti-FGF Therapies in Imatinib-Resistant Gastrointestinal Stromal Tumors (GIST) Lacking Secondary KIT Mutations

Project description:Acquired resistance of gastrointestinal stromal tumors (GISTs) to imatinib mesylate (IM) is one of the most critical challenges in GIST therapy. Here we show that a long-term culture of GIST T-1 cells with IM induces clonal heterogeneity resulting in the appearance of cancer cells exhibiting activation of the FGFR-signaling pathway which was associated with KIT loss. The first one was due to the overexpression of FGFR1/2 and increased production of FGF-2 ligand. These events maintained GIST resistance to IM and rendered these GIST cells highly sensitive to all types of pan-FGFR-inhibitors used in the current study. Knockout of FGFR2 in this GIST subclone significantly attenuated pro-apoptotic and anti-proliferative activities of infigratinib (BGJ 398) both in vitro and in vivo, thereby suggesting the activation of FGFR-signaling pathway via FGFR2-mediated axis as the predominant molecular mechanism in these GIST cells. Collectively, the extended inhibition of KIT-signaling in GISTs induces clonal heterogeneity of cancer cells and might change the tumor’s sensitivity to FGFR-inhibitors due to selection of cancer cells with an FGFR-overactivated pathway.

2023-11-09 | GSE247170 | GEO

Gene expression analysis of imatinib-resistant GIST

Project description:To reveal mechanisms for acquired imatinib resistance in gastrointestinal stromal tumor (GIST), we have analyzed several cell lines with resistance to imatinib.

2016-12-27 | GSE69465 | GEO

Expression Data from Gastrointestinal Stromal Tumor (GIST) Cell Lines

Project description:Activating mutations in either KIT or PDGFRA are present in approximately 90% of gastrointestinal stromal tumors (GISTs). Although treatment with the KIT and PDGFR inhibitor imatinib can control advanced disease in about 80% of GIST patients, the beneficial effect is not durable. Here, we report that ligands from the FGF family reduced the effectiveness of imatinib in GIST cells, and FGF2 and FGFR1 are highly expressed in all primary GIST samples examined. The combination of KIT and FGFR inhibition showed increased growth inhibition in imatinib-sensitive GIST cell lines in the presence or absence of added FGF2 in vitro, and delayed tumor regrowth in vivo. In addition, inhibition of mitogen-activated protein kinase (MAPK) signaling by imatinib was not sustained in GIST cells. An extracellular signal-regulated kinase (ERK) rebound occurred through activation of FGF signaling, and was repressed by FGFR1 inhibition. Downregultation of Sprouty proteins played a role in the imatinib-induced feedback activation of FGF signaling in GIST cells. We used micorarrays to quantify the gene expression levels in GIST cell lines.

2015-01-08 | GSE64762 | GEO

Expression Data from Gastrointestinal Stromal Tumor (GIST) Cell Lines

2015-01-08 | E-GEOD-64762 | biostudies-arrayexpress

Affymetrix human DMET Plus array in GIST patients treated with imatinib

Project description:To understand the contribution of germline DNA polymorphisms discriminating between imatinib clinical outcome and toxicity, 38 GIST patients (all with KIT exon 11 mutation) treated with imatinib were analyzed through Affymetrix human DMET Plus array.

2019-01-01 | GSE119558 | GEO

Identification of transcriptional difference between Imatinib-sensitive and resistant patients with gastrointerstinal stromal tumor (GIST)

Project description:Purpose: The goals of this study are to characterize the transcriptional dysregulation of GIST. More importantly, the transcriptome differences betweeen Imatinib-sensitive and resistant patients are compared to identify RNAs that may impact Imatinib resistance. Methods: High-throughput RNA sequencing (RNA-seq) was employed to capture the transcriptional changes in GIST compared to normal samples. RSEM was used to quantify gene expression and DESeq2 was utilized to compared expression changes between different sample groups.

2021-07-29 | GSE155800 | GEO

The effect of imatinib therapy on tumor associated macrophages (TAMs) in murine gastrointestinal stromal tumor (GIST)

Project description:The gene expression profile of TAMs sorted from vehicle control tumors in GIST mice (Sommer et al, PNAS 2003) was compared to TAMs sorted from mice after 2 weeks of imatinib therapy The Affymetrix Mouse Genome 430A 2.0 platform was used

2013-11-20 | GSE51698 | GEO

Imatinib Treatment of GIST882

Project description:Gastrointestinal Stromal Tumor frequently harbor mutations in the KIT receptor tyrosine kinase and depend on its activity for growth. This underlies the efficacy of imatinib, a inhibitor of KIT activity, in GIST management. GIST882 is a patient derived GIST cell line that harbor a K640E exon 13 KIT mutation and is sensitive to imatinib treatment. To analyze the downstream effect of KIT inhibition, GIST882 cells were treated for 8 hours with 1μM Imatinib.

2010-10-13 | GSE22433 | GEO

Genome wide analysis of mouse gastrointestinal stromal tumors (GIST) in a mouse model of spontaneous GIST.

Project description:Analysis of mouse GIST tumors at the gene expression level. The purpose of the study was to identify immunomodulatory genes in mouse GIST tumors after in vivo treatment with the specific tyrosine kinase inhibitor imatinib mesylate. Total RNA obtained from mouse GIST tumors after in vivo treatment with imatinib or vehicle control injected intraperitoneally.

2011-12-31 | E-GEOD-30416 | biostudies-arrayexpress

Genome wide analysis of mouse gastrointestinal stromal tumors (GIST) in a mouse model of spontaneous GIST.

2011-12-31 | GSE30416 | GEO