{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001001844"],"host":["EGA"],"description":["EGA study EGAS00001001844"],"dataset_title":["Exome"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["short stature, lambdatop, HBGFR, HRTFDS, SOFT, Spindle Cell Sarcomas, dFGFR, dev, CD331, KAL2, soft, and hypotrichosis, x1fgfr, CEK, Soft Tissue Sarcoma, kal2, DFGF-R1, HH2, Eask, tumour of soft tissue and skeleton, bfgfr, Btl, DFR2, Fgf-r, FLG, malignant., treatment, Sarcomas, flt-2, 0844/01, cek, fgfr1, BFGFR, FGFBR, Tissue, Hspy, tumor of soft tissue and skeleton, fgfr-1, X1FGFR, Dfr-2, CG6714, flg, BTL/FGFR2, Sarcoma, FGFR, OGD, disease management, Therapies, onychodysplasia, AW208770, Spindle Cell Sarcoma, Tk2, connective and soft tissue neoplasm, Flt-2, FGFR1, Therapy, sarcoma, FLT2, ogd, FLT-2, malignant, D-FGFR, bFGF-R-1, dtk2, xfgfr1, Fgfr-1, N-SAM, fgf-r, XFGFR-1, DmHD-311, Epithelioid Sarcomas, flt2, simple tissue, PIX2, WDR51A, Epithelioid, Spindle Cell, DmelCG32134, FGFR-1, Soft Tissue Sarcomas, XFGFRA2, MFR, sarcoma of the soft tissue and bone, Treatments, CG32134, CT20816, Therapeutic, sarcoma of soft tissue and bone, Epithelioid Sarcoma, mesenchymal tumor, c-fgr, facial dysmorphism, HD-311, Treatment, l(3)00208, Dtk2, Soft Tissue"],"description_synonyms":["Experimental Designs, Comparative Genome, Ribonucleic, DmErk, extracellular signal-regulated kinase activity, pp44mapk, Materials, short stature, Product, Adjustments, RNA Sequence Determination, lambdatop, HBGFR, SOFT, Sequence Determination, RNA Sequence, Design, Error Sources, dev, Research Subject Recruitment, 5-dimethoxyphenyl)ethyl)-2H-pyrazol-3-yl)-4-(3, soft, Prp4 protein kinase activity, x1fgfr, LeMPK3, CEK, Method, ATP-protein transphosphorylase activity, p44mpk, ATP:protein phosphotransferase (non-specific) activity, Line, Dp38, Eask, Analysis, SAPK2, SEM, Sem, Non Polyadenylated, Fgf-r, FLG, MAP-k, Selection, cek, Analyses, pp42, Matched Group, C2, Tissue, Matched, Dsor2, Hspy, fgfr-1, Myxoid, sem, Sequence Determinations, Subject Recruitment, ISH, flg, BTL/FGFR2, allergic reaction, set, medicine, Reporting, Role Concepts, (+)-Staurosporine, onychodysplasia, Homo sapiens disease, Tk2, connective and soft tissue neoplasm, single organism signaling, Data Reporting, ERK-A, p82 kinase activity, Research Subject Selection, dpERK, dpErk, Research Technic, Polyadenylated, Research Methodology, Recruitment, ERK-1, familial, betaIIPKC, bFGF-R-1, DmMAPK, PMK-2, dp-ERK, PMK-1, Research Proposal, PMK-3, Selections, Wee-kinase activity, Experimental, Role Concept, XFGFR-1, ES, Role, pMAPK, pMapK, simple tissue, Technics, Ribonucleic acids, Problem Formulation, Subject Selection, Volunteers Selection, Polyadenylated Messenger RNA, Acid, Non Polyadenylated mRNA, DmERKA, Spindle Cell, protein_coding_transcript, rl/MAPK, FGFR-1, Array Based Comparative Genomic Hybridization, non-specific serine/threonine protein kinase activity, l(2)41Ac, INSDC_feature:gene, Mtap2k, surveillance, Non-Polyadenylated mRNA, Formulations, Epithelioid Leiomyosarcomas, CT34260, Comparative Genomic, dpERk, Material, Epithelioid Sarcoma, serine-specific protein kinase activity, SAPK, HIPK2, cytidine 3', l(3)00208, Subjects Selections, Wee 1-like kinase activity, mitogen-activated protein kinase 1, Data Adjustments, Poly(A) RNA, Soft Tissue, p44erk1, glycogen synthase A kinase activity, HRTFDS, glycogen synthase kinase 3 activity, Spindle Cell Sarcomas, Matched Groups, number, 12559, stalk, phosphorylase b kinase kinase activity, KAL2, EK2-1, Adjustment, Soft Tissue Sarcoma, sensitive, Sources, kal2, Gene Products, disease or disorder, Prkm3, Leiomyosarcoma, ribosomal protein S6 kinase II activity, bfgfr, Technique, Erk, ERK, PRKM1, Sarcomas, PRKM3, PRKM2, protein-serine kinase activity, fgfr1, occurrence, FGFBR, prevalence, STK32, messenger RNA, Selection Criteria, tumor of soft tissue and skeleton, Sequencing, culm, CG6714, Research Strategy, erk, template RNA, drugs, protein-cysteine kinase activity, Selection for, FGFR, OGD, Hpr kinase activity, rll, STK26, Spindle Cell Sarcoma, p38-2, constitutitional genetic, myelin basic protein kinase activity, Pharmaceuticals, Sequence Analyses, Products, FLT2, RNA, Esrk1, grupo, Genomic Hybridizations, RNA Sequence Determinations, ogd, FLT-2, stress-activated kinase activity, disorders, Messenger RNA, MAP-2 kinase activity, RNS, dtk2, protein serine kinase activity, Cell, xfgfr1, protein phosphokinase activity, N-SAM, Concept, Research Strategies, fgf-r, PKA, Myxoid Leiomyosarcoma, PKC, ARSC1, Epithelioid Sarcomas, Poly(A)+ mRNA, stress-activated protein kinase activity, chemical analysis, mapk2, mapk1, INSDC_feature:mRNA, condition, flt2, Comparative Genome Hybridizations, outbreaks, protein kinase p58 activity, epitheliocyte, serine/threonine protein kinase activity, CG12559, Pharmaceutic Preparations, mRNA, underdeveloped, ensemble, Leiomyosarcomas, increased number, dpERK1, Specificity, Soft Tissue Sarcomas, Research Designs, Research Technics, Ribonucleic Acid, MFR, Selection for Treatments, dsk1, 5'-cyclic monophosphate-responsive protein kinase activity, atypical PKC activity, CG32134, CT20816, Data Adjustment, signalling process, Error, dpMAPK, mesenchymal tumor, epidemics, Dtk2, Pharmaceutical Products, Strategy, Polyadenylated mRNA, hereditary, p44mapk, protein serine-threonine kinase activity, SAP kinase activity, MAPK 1, glycogen synthase kinase activity, Selection for Treatment, Research Technique, Problem Formulations, protein kinase A activity, determination, Recruitments, Mpk2, dFGFR, STS, Subject Selections, p42mapk, Technic, Staurosporin, CD331, SR2-1, Techniques, P44ERK1, diseases, Roles, Pharmaceutical Product, DFGF-R1, kinase-related transforming protein, Concepts, diseases and disorders, In Situ, mitogen-activated protein kinase activity, tumour of soft tissue and skeleton, mpk1, Btl, DFR2, RNA Gene Products, Experimental Design, multicellular organismal biosynthetic process, in situ hybridization, Group, increased, single-organism biosynthetic process, human disease, Erk/Map kinase, Determination, Polyadenylated Messenger, long, Research Subject Recruitments, AM-2282, ASC, Designs, hypoplasia, DERK-A, Groups, E(sina)7, experimental design, short telomere syndrome, Rl, Dfr-2, ArsC, Raf kinase activity, ARSC, genetic, Sarcoma, MP kinase activity, serine kinase activity, Genome Hybridization, DERK, atypical protein kinase C activity, Pharmaceutical, leiomyosarcoma - not uterine, comparative genomic hybridization, Research Techniques, Comparative Genomic Hybridizations, MBP kinase II activity, mitogen-activated S6 kinase activity, ATP - protein phosphotransferase (MAPKK-activated) activity, protein-aspartyl kinase activity, dERK, Patient Recruitment, Flt-2, MNK1, Mnk1, MAP kinase 2 activity, Array-Based Comparative Genomic Hybridization, Hybridization, ribose nucleic acid, Mapk, Comparative, frequency, ribonucleic acids, Erk1, Research Proposals, ERK1, ERK2, mapk1a, Selection of Research Volunteers, Hybridizations, results, Fgfr-1, Determinations, M phase-specific cdc2 kinase activity, shortened, Research Subject, epithelial, mapk1b, MapK, MAPK, Ribonukleinsaeure, Diseases, Epithelioid Leiomyosarcoma, pentosenucleic acids, Genetic Materials, Pharmaceutic, PIX2, Problem, serine protein kinase activity, erk2, mapk, Genetic Material, Lines, ERKa, phosphorylase B kinase kinase activity, SSDD, BcDNA:RE08694, protein glutamyl kinase activity, DmelCG32134, l(2R)EMS45-39, DmelCG12559, p38, XFGFRA2, sarcoma of the soft tissue and bone, N-(5-(2-(3, morbidity, Treatments, DpErk, DpERK, ErkA, ERKA, disease, metastatic, hydroxyalkyl-protein kinase activity, HUMKER1A, WEE1Hu, sarcoma of soft tissue and bone, Patient, Specificity and Sensitivity, epsilon PKC, c-fgr, antibiotic AM 2282, Genome Hybridizations, facial dysmorphism, P44MAPK, p44, microarray, Cistron, medical condition., inherited genetic, short, accessory, pERK, Gruppe, ribosomal S6 protein kinase activity, other disease, calcium/phospholipid-dependent protein kinase activity, GroupII, leiomyosarcoma, Gene, Scoring Method, supernumerary, presence, Myxoid Leiomyosarcomas, and hypotrichosis, Research Volunteers Selection, HS44KDAP, reduced, Research Volunteers Selections, Scoring Methods, Array Comparative Genomic Hybridization, Messenger, Subjects Selection, serine(threonine) protein kinase activity, HH2, tiny, Research Subject Selections, sensitivity, T-antigen kinase activity, Drugs, galactosyltransferase-associated kinase activity, flt-2, Methodology, 0844/01, Genetic, Scoring, Research, Criteria, Proposals, Subject Recruitments, BFGFR, xp42, stubby, Hybridization in Situ, chromosomal comparative genomic hybridization, leiomyosarcoma (excluding uterine leiomyosarcoma), X1FGFR, p42 mitogen-activated protein kinase activity, CG18732, ATP:protein phosphotransferase (MAPKK-activated) activity, Non-Polyadenylated RNA, non-neoplastic, protein kinase (phosphorylating) activity, Erk-1, RNA Sequence Analyses, Raf-1, grupos, Clients, Error Source, RNA Sequencing, Sensitivity, disorder, In Situ Hybridizations, DmERK-A, Preparation, AW208770, Strategies, casein kinase (phosphorylating) activity, incidence, FGFR1, small, sarcoma, 5-diemthylpiperazin-1-yl)benzamide, ert1, axis, malignant, drug, prkm2, D-FGFR, Cell Lines, prkm1, CT39192, Selection of Subjects, Formulation, Comparative Genome Hybridization, MAP kinase 1, Cistrons, Client, group, p38delta, count in organism, twitchin kinase activity, DmHD-311, yeast nucleic acid, AP50 kinase activity, MBP kinase I activity, Polyadenylated RNA, WDR51A, Epithelioid, Proposal, Methods, Xp42, threonine-specific protein kinase activity, ribonucleic acid, Poly(A)+ RNA, Poly(A) Tail, mitogen activated kinase activity, Source, Non Polyadenylated RNA, Su(Raf)2B, Non-Polyadenylated, Rest, XLI, patient, EY2-2, MAPK1, endemics, Drug, present in greater numbers in organism, Preparations, D-ERK, Data, Ert2, Genomic Hybridization, ERT2, RNA Sequence Analysis, p44-MAPK, cardinality, p44-ERK1, HD-311, Treatment, assay, groupe, Pharmaceutical Preparation, MAP kinase 1 activity, A-kinase activity"],"additional_accession":[]},"is_claimable":false,"name":"Targeting FGFR1 for treatment of soft-tissue sarcoma (H021)","description":"Purpose: Altered FGFR1 signaling has emerged as therapeutic target in various epithelial malignancies. In contrast, the role of FGFR1 in soft-tissue sarcoma (STS) has not been established. Prompted by the detection and subsequent therapeutic inhibition of amplified FGFR1 in a patient with metastatic leiomyosarcoma, we investigated the oncogenic properties and potential as drug target of FGFR1 in STS.Experimental Design: The frequency of FGFR1 amplification and overexpression, as assessed by fluorescence in situ hybridization, microarray-based comparative genomic hybridization and mRNA expression profiling, SNP array profiling, and RNA sequencing, was determined in three independent patient cohorts. The sensitivity of STS cell lines with or without FGFR1 alterations to genetic and pharmacologic FGFR1 inhibition and the signaling pathways engaged by FGFR1 were investigated using short-term viability assays, long-term colony formation assays, and biochemical analysis.Results: Increased FGFR1 copy number was detected in 74 of 190 (38.9%; Cohort 1), 13 of 79 (16.5%; Cohort 2), and 80 of 254 (31.5%; Cohort 3) patients. FGFR1 overexpression occurred in 16 of 79 (20.2%, Cohort 2) and 39 of 254 (15.4%; Cohort 3) patients. Targeting of FGFR1 by short hairpin RNA-mediated knockdown and different small-molecule inhibitors (PD173074, AZD4547, BGJ398) revealed that the requirement for FGFR1 signaling in STS cells is primarily dictated by FGFR1 expression levels, and identified the MAPK-ERK1/2 axis as critical FGFR1 effector pathway.Conclusion: These data identify FGFR1 as driver gene in multiple STS subtypes and support FGFR1 inhibition, guided by patient selection according to FGFR1 expression and monitoring of MAPK-ERK1/2 signaling, as therapeutic option in this challenging group of diseases.H021","dates":{"updated":"2017-07-26 15:39:26"},"accession":"EGAS00001001844","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001002159","EGAC00001000452"]}}