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Ref Type Journal Article
PMID (26036639)
Authors Kunstlinger H, Fassunke J, Schildhaus HU, Brors B, Heydt C, Ihle MA, Mechtersheimer G, Wardelmann E, Buttner R, Merkelbach-Bruse S
Title FGFR2 is overexpressed in myxoid liposarcoma and inhibition of FGFR signaling impairs tumor growth in vitro.
Journal Oncotarget
Vol 6
Issue 24
Date 2015 Aug 21
URL
Abstract Text Myxoid liposarcomas account for more than one third of liposarcomas and about 10% of all adult soft tissue sarcomas. The tumors are characterized by specific chromosomal translocations leading to the chimeric oncogenes FUS-DDIT3 or EWS1R-DDIT3. The encoded fusion proteins act as aberrant transcription factors. Therefore, we implemented comparative expression analyses using whole-genome microarrays in tumor and fat tissue samples. We aimed at identifying differentially expressed genes which may serve as diagnostic or prognostic biomarkers or as therapeutic targets. Microarray analyses revealed overexpression of FGFR2 and other members of the FGF/FGFR family. Overexpression of FGFR2 was validated by qPCR, immunohistochemistry and western blot analysis in primary tumor samples. Treatment of the myxoid liposarcoma cell lines MLS 402 and MLS 1765 with the FGFR inhibitors PD173074, TKI258 (dovitinib) and BGJ398 as well as specific siRNAs reduced cell proliferation, induced apoptosis and delayed cell migration. Combination of FGFR inhibitors with trabectedin further increased the effect. Our study demonstrates overexpression of FGFR2 and a functional role of FGFR signaling in myxoid liposarcoma. As FGFR inhibition showed effects on proliferation and cell migration and induced apoptosis in vitro, our data indicate the potential use of FGFR inhibitors as a targeted therapy for these tumors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 amp stomach cancer sensitive PD173074 Preclinical - Cell culture Actionable In a preclinical study, PD173074 inhibited proliferation of a gastric cancer cell line harboring FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp myxoid liposarcoma sensitive Infigratinib Preclinical Actionable In a preclinical study, Infigratinib (BGJ398) increased apoptosis, and inhibited cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp stomach cancer sensitive Infigratinib Preclinical Actionable In a preclinical study, Infigratinib (BGJ398) inhibited proliferation of gastric cancer cell lines harboring FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp myxoid liposarcoma sensitive PD173074 + Trabectedin Preclinical Actionable In a preclinical study, PD173034 and Yondelis (trabectedin) worked synergistically to increase apoptosis, inhibit cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp myxoid liposarcoma sensitive PD173074 Preclinical Actionable In a preclinical study, PD173074 increased apoptosis, inhibited cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp myxoid liposarcoma sensitive Infigratinib + Trabectedin Preclinical Actionable In a preclinical study, Infigratinib (BGJ398) and Yondelis (trabectedin) worked synergistically to increase apoptosis, inhibit cell proliferation and migration of myxoid liposarcoma cell lines harboring FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp myxoid liposarcoma sensitive Dovitinib + Trabectedin Preclinical Actionable In a preclinical study, Dovitinib (TKI258) and Yondelis (trabectedin) worked synergistically to increase apoptosis, inhibit cell proliferation and migration of myxoid liposarcoma cell lines harbors FGFR2 amplification in culture (PMID: 26036639). 26036639
FGFR2 amp myxoid liposarcoma sensitive Dovitinib Preclinical Actionable In a preclinical study, Dovitinib (TKI258) increased apoptosis, inhibited cell proliferation and migration of myxoid liposarcoma cell lines harbors FGFR2 amplification in culture (PMID: 26036639). 26036639