title: The second European interdisciplinary Ewing sarcoma research summit--A joint effort to deconstructing the multiple layers of a complex disease.
abstract: Despite multimodal treatment, long term outcome for patients with Ewing sarcoma is still poor. The second "European interdisciplinary Ewing sarcoma research summit" assembled a large group of scientific experts in the field to discuss their latest unpublished findings on the way to the identification of novel therapeutic targets and strategies. Ewing sarcoma is characterized by a quiet genome with presence of an EWSR1-ETS gene rearrangement as the only and defining genetic aberration. RNA-sequencing of recently described Ewing-like sarcomas with variant translocations identified them as biologically distinct diseases. Various presentations adressed mechanisms of EWS-ETS fusion protein activities with a focus on EWS-FLI1. Data were presented shedding light on the molecular underpinnings of genetic permissiveness to this disease uncovering interaction of EWS-FLI1 with recently discovered susceptibility loci. Epigenetic context as a consequence of the interaction between the oncoprotein, cell type, developmental stage, and tissue microenvironment emerged as dominant theme in the discussion of the molecular pathogenesis and inter- and intra-tumor heterogeneity of Ewing sarcoma, and the difficulty to generate animal models faithfully recapitulating the human disease. The problem of preclinical development of biologically targeted therapeutics was discussed and promising perspectives were offered from the study of novel in vitro models. Finally, it was concluded that in order to facilitate rapid pre-clinical and clinical development of novel therapies in Ewing sarcoma, the community needs a platform to maintain knowledge of unpublished results, systems and models used in drug testing and to continue the open dialogue initiated at the first two Ewing sarcoma summits.
authors.affiliation: Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, Vienna, Austria.|Department of Pediatrics, Medical University Vienna, Vienna, Austria.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Kovar
authors.affiliation: Departments of Pediatrics, Molecular Biology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: James
authors.initials: J
authors.lastname: Amatruda
authors.affiliation: Museum National d'Histoire Naturelle, INSERM U1154, CNRS 7196, Paris, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Brunet
authors.affiliation: Children's Cancer Research Center and Department of Pediatrics, Klinikum rechts der Isar, Technical University and Comprehensive Cancer Center Munich (CCCM), Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.affiliation: Unidad de Tumores Sólidos Infantiles, Área de Genética Humana, Instituto de Investigación de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Florencia
authors.initials: F
authors.lastname: Cidre-Aranaz
authors.affiliation: Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocio University Hospital /CSIC/University de Sevilla, Department of Pathology, Seville, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: de Alava
authors.affiliation: University Children´s Hospital Muenster, Pediatric Hematology and Oncology, Muenster, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Dirksen
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.|Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: Wietske
authors.initials: W
authors.lastname: van der Ent
authors.affiliation: Van Andel Institute, Center for Cancer and Cell Biology and Helen DeVos Children's Hospital, Grand Rapids, MI, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Grohar
authors.affiliation: Laboratory for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, Munich, Germany.
authors.forename: Thomas G P
authors.initials: TG
authors.lastname: Grünewald
authors.affiliation: Center for Cancer Rearch, NCI, NIH, Bethesda, MA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Helman
authors.affiliation: Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Houghton
authors.affiliation: VTT Technical Research Centre of Finland Ltd, Espoo, Finland.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Iljin
authors.affiliation: Institute of Bioinformatics, Faculty of Medicine, University of Muenster, Muenster, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Korsching
authors.affiliation: Department of Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.affiliation: Department of Pediatrics and Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lawlor
authors.affiliation: Center for Childhood Cancer and Blood Disorders, Nationwide Children's Hospital, and the Division of Pediatric Hematology/Oncology/BMT, The Ohio State University, Columbus, OH, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lessnick
authors.affiliation: Department of Sarcoma Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ludwig
authors.affiliation: Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Meltzer
authors.affiliation: Pediatric Oncology and Hematology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Metzler
authors.affiliation: Department of Pediatric Oncology, Sant Joan de Déu Hospital, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Mora
authors.affiliation: Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria.|Institute of Animal Breeding and Genetics, University of Veterinary Medicine and Medical University, Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.affiliation: Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: University of Glasgow, School of Mathematics and Statistics, Glasgow, UK.
authors.forename: Theodore
authors.initials: T
authors.lastname: Papamarkou
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Branka
authors.initials: B
authors.lastname: Radic Sarikas
authors.affiliation: INSERM UMR957, Université de Nantes, Nantes, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Rédini
authors.affiliation: Children's Cancer Research Center and Department of Pediatrics, Klinikum rechts der Isar, Technical University and Comprehensive Cancer Center Munich (CCCM), Munich, Germany.
authors.forename: Guenther H S
authors.initials: GH
authors.lastname: Richter
authors.affiliation: University Children´s Hospital Muenster, Pediatric Hematology and Oncology, Muenster, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rossig
authors.affiliation: Department of Pediatrics Research, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Keri
authors.initials: K
authors.lastname: Schadler
authors.affiliation: Department of Oncology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
authors.forename: Beat W
authors.initials: BW
authors.lastname: Schäfer
authors.affiliation: CRS Development of Biomolecular Therapies, Experimental Oncology Lab, Rizzoli Institute, Bologna, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Sheffield
authors.affiliation: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis,TN, USA.
authors.forename: Anang
authors.initials: A
authors.lastname: Shelat
authors.affiliation: Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: Ewa
authors.initials: E
authors.lastname: Snaar-Jagalska
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.
authors.forename: Poul
authors.initials: P
authors.lastname: Sorensen
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Stegmaier
authors.affiliation: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stewart
authors.affiliation: Division of Hematology and Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sweet-Cordero
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.affiliation: Sarcoma Research Group, Molecular Oncology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Tirado
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Tirode
authors.affiliation: Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Toretsky
authors.affiliation: Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Tsafou
authors.affiliation: Department of Oncology, Georgetown University School of Medicine, Washington, DC, USA.
authors.forename: Aykut
authors.initials: A
authors.lastname: Üren
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.|INSERM, U900, Paris, France.|Ecole des Mines ParisTech, Fontainbleau, France.
authors.forename: Andrei
authors.initials: A
authors.lastname: Zinovyev
authors.affiliation: INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000378:metabolism*; D012512:Sarcoma, Ewing / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
chemical_list: C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS
keywords: Ewing sarcoma; development; epigenetics; microenvironment; therapy