EGAGenomicsOtherhttps://ega-archive.org/studies/EGAS00001005836EGAEGA study EGAS00001005836Dataset for Sarcoma RNA sequencing linked from study EGAS00001004813Paired Exome sequencing of Sarcoma tumor and controlPaired WGS samples (tumor and control) of one Sarcoma caseDataset for Sarcoma-WGS linked from study EGAS00001004813Dataset for Sarcoma-WES linked from study EGAS00001004813restrictedEGAGW786034B, Sarcomas, sarcoma, Hpo, Spindle Cell, CG11228, Gene Expressions, pazopanibum, GW 786034B, malignant, Spindle Cell Sarcomas, DmelCG11228, Soft Tissue Sarcomas, Gene, GW 780604, GW786034, GW-780604, tumor of soft tissue and skeleton, sarcoma of the soft tissue and bone, Expressions, Votrient, MST2, GW-786034B, Sarcoma, dMST, MST., GW 78603, sarcoma of soft tissue and bone, Soft Tissue Sarcoma, Epithelioid Sarcoma, GW780604, pazopanib, Epithelioid Sarcomas, mesenchymal tumor, hipo, Expression, Spindle Cell Sarcoma, tumour of soft tissue and skeleton, Soft Tissue, connective and soft tissue neoplasm, EpithelioidtrkC, Ras1/RAs85D, 70zpep, RAS, Ras, PEP/X4, PP14, Materials, short stature, Activity, Product, determination, DmelCG30170, SOFT, LYP2, b(2)gcn, Feature, LYP1, Gene Expression Profile, E(sev)3C, Profiles, KDR, Ras-1, Tumor, JTK13, DmelCG6143, soft, ras, Associations, Pharmaceutical Product, Pop, Whole Transcriptome, Transcriptome Sequencing, Event-Free Survival, IGFIR, tumour of soft tissue and skeleton, Non Polyadenylated, D-Ras1, adult, CD221, treatment, igf-1r, LyP, skeletal, me75, Receptor tyrosine kinase, RTK, pazopanibum, IGFR, Genomes, GW 786034B, Complete Exome Sequencing, Polyadenylated Messenger, C1, Whole Transcriptome Sequencing, Tissue, sVEGFR-2, ras85B, GW 780604, X4/PEP, ras85D, PEPPER, Signatures, Ntrk3_tv3, D17Mit170, T1, genetic, LYP, Sarcoma, GW 78603, Lymphoid phosphatase, medicine, malignant neoplasm, Expression Signature, Pharmaceutical, PrEP, disease management, Naturalistic Observation Study, Therapies, Transcriptomes, TrkC, TRKC, onychodysplasia, Malignancies, PAEG, Krd-1, F12B17_170, fs(2)eo-C, connective and soft tissue neoplasm, Tumors, Therapy, l(3)s1747, CG6143, Ras1, RAS1, Polyadenylated, Exome, Expression Profiles, familial, ben(2)gcn, VEGFR, Tl3, PEPINO, Votrient, Tl2, Gene Expression, GW-786034B, Flk-1, Benign, Natural Experiment Study, FLK1, Expression Signatures, RENBP, Flk1, dRas85D, 3.1.3.48, Genetic Materials, p21[Ras1], A330103N21Rik, simple tissue, Pharmaceutic, D930020L01, CD309, dRas1, dRAS1, PIX2, ras1, Expression Profile, Adults, Dras85D, Genetic Material, 2-(phosphonooxy)-2-propenoic acid, Transcriptome Profiles, Polyadenylated Messenger RNA, VEGFR2, protein-tyrosine kinase receptor flk-1, Complete Transcriptome, PEST-domain phosphatase, Non Polyadenylated mRNA, bcgn, Spindle Cell, protein_coding_transcript, IGFIRC, F20B18.110, gp145(trkC), D-ras1, Igfr1, F20B18_110, C-ras1, Benign Neoplasms, common, Dm Ras1, AI047692, whole genome, sarcoma of the soft tissue and bone, Features, Treatments, Non-Polyadenylated mRNA, GD, l(3)06677, Malignant Neoplasms, AGE, Atlases, RasI, GdA, GdF, antagonists and inhibitors, sarcoma of soft tissue and bone, Patient, PNBP, Material, Epithelioid Sarcoma, pazopanib, facial dysmorphism, Whole Exome Sequencing, Protein-tyrosine kinase receptor flk-1, Cistron, inherited genetic, GdS, Transcriptome Sequencings, PEP, Poly(A) RNA, cg10331, Soft Tissue, RasV12, Complete Exome, Transcriptome Profile, dRas, Neoplasms, Spindle Cell Sarcomas, Prospective, Benign Neoplasm, gcn, Gene, DRAS1, DmelCG9375, pep, Malignant, and hypotrichosis, fs(2)eo6, Dras1, CG30170, D-Ras, Soft Tissue Sarcoma, Messenger, Survival, Prospective Study, Studies, Low, PHOSPHOENOLPYRUVATE, Dras, GW786034B, Drugs, ras 1, Sarcomas, study, WES, Complete, dras1, Exome Sequencings, Genetic, Natural Experiment, Malignancy, xigf1r, Profile, inhibiteur, messenger RNA, GW786034, tumor of soft tissue and skeleton, FLK-1, Event-Free, Ras[V12], EK3-4, AW125844, CG10331, Sequencing, CG10330, DRas, DRas85D/Ras, Neoplasias, Study, Ras 85D, template RNA, drugs, Whole Exome, Vegfr-2, 2.7.10.1, inhibidor, Pharmaceuticals., Event Free Survival, PASTICCINO 2, GW780604, Clients, Whole, Ly73, BGCN, Characteristics, Preparation, Spindle Cell Sarcoma, constitutitional genetic, receptor tyrosine kinase, kinase NYK, Hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, Pharmaceuticals, Cancer, inhibitors, Products, WGS, sarcoma, RNA, Transcriptome, Malignant Neoplasm, Complete Exome Sequencings, cou, CG9375, RnBP, malignant, drug, Bgcn, D10Wsu136e, GlcNAc 2-epimerase, Messenger RNA, inhibitor, b(2)cgn, GW-780604, 6130401C07, D-ras-1, Muscle, Cistrons, Client, Kinase insert domain receptor, Progression Free Survival, E(faf), Exome Sequencing, fs(3)05703, N-acetyl-D-glucosamine 2-epimerase, Lr, MT, Characteristic, Epithelioid Sarcomas, Poly(A)+ mRNA, Gene Expression Signatures, chemical analysis, hyft, S35097, Neoplasm, INSDC_feature:mRNA, p100, Gene Expression Signature, rare (European definition), Polyadenylated RNA, WDR51A, Epithelioid, antagonists, Progression-Free, F12B17.170, RAS85D, primary cancer, Poly(A)+ RNA, Dmras85D, Complete Transcriptome Sequencing, Pharmaceutic Preparations, mRNA, Poly(A) Tail, Ptpn8, Non-Polyadenylated, Soft Tissue Sarcomas, fs(2)eoQS2, patient, Cancers, Su(tor)3-2, malignant tumor, IGF-1R, Drug, kinase insert domain receptor, Preparations, 2-PHOSPHOENOLPYRUVIC ACID, Therapeutic, Gene Expression Profiles, mesenchymal tumor, Fetal liver kinase 1, Bra, renin-binding protein, Treatment, fetal liver kinase 1, assay, PE, VEGFR-2, Signature, AI450383, variable, PTPN8, Pharmaceutical Products, Polyadenylated mRNA, hereditary, General activity, Neoplasia, Pharmaceutical PreparationfalseGene expression-based prediction of pazopanib efficacy in sarcoma (HIPO, H021)The multi-receptor tyrosine kinase (RTK) inhibitor pazopanib is approved for the treatment of advanced non-adipocytic soft-tissue sarcoma and has also shown activity in other sarcoma subtypes. However, its clinical efficacy is highly variable, and no reliable predictors exist to date to select patients who are most likely to benefit from this drug. We analyzed the molecular profiles and clinical outcomes of pazopanib-treated sarcoma patients enrolled in a prospective observational study by the German Cancer Consortium, DKTK MASTER, that employs whole-genome/exome sequencing (WGS/WES) and transcriptome sequencing to inform the care of adults with advanced cancer across histologies who are younger than 51 and patients with rare tumors, including rare subtypes of more common entities, regardless of age.​ Among a total of 109 patients with available WGS/WES data, there was no correlation between clinical parameters, specific genetic alterations, or mutational signatures and clinical outcome. In contrast, analysis of a subcohort of 62 patients who underwent molecular analysis before pazopanib treatment and had transcriptome sequencing data available showed that mRNA levels of NTRK3 (hazard ratio [HR]=0.53, p=0.021), IGF1R (HR=1.82, p=0.027), and KDR (HR=0.50, p=0.011) were independently associated with progression-free survival (PFS). Based on the expression of these RTK genes, i.e., the features NTRK3-high, IGF1R-low, and KDR-high, we developed a pazopanib efficacy predictor (PEP) that stratified patients into three groups with significantly different PFS (p<0.0001). Application of the PEP to an independent cohort of pazopanib-treated sarcoma patients from DKTK MASTER (n=43) confirmed its potential to separate patient groups with significantly different PFS (p=0.02), whereas no such association was observed in sarcoma patients from DKTK MASTER (n=77) or The Cancer Genome Atlas sarcoma cohort (n=256) who were not treated with pazopanib. A score based on the combined expression of NTRK3, IGF1R, and KDR allows identification of sarcoma patients with good, intermediate, and poor outcome following pazopanib therapy and warrants investigation as a predictive tool in prospective studies to optimize the use of this drug in the clinic.2023-04-27 12:17:39EGAS000010058369606EGAD00001010258EGAD00001010278EGAD00001010257EGAD00001010277EGAD00001010276EGAC00001000452