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Flierl, Dominik Bernhard ; Alt, Christopher ; Antičić, Tome ; Baatar, B. ; Barna, Daniel ; Bartke, Jerzy ; Betev, Latchezar ; Białkowska, Helena ; Billmeier, Anja ; Blume, Christoph ; Boimska, Bożena ; Botje, Michiel ; Bracinik, Juraj ; Bramm, Roland ; Brun, René ; Bunčić, Predrag ; Černý, Vladimír ; Christakoglou, Panagiotis ; Chvala, Ondrej ; Cramer, John G. ; Csato, Péter ; Darmenov, Nikolay ; Dimitrov, Anton ; Dinkelaker, Peter ; Eckardt, Volker ; Farantatos, Gerassimos ; Fodor, Zoltán ; Foka, Panagiota ; Freund, Peter ; Friese, Volker ; Gal, József ; Gaździcki, Marek ; Georgopoulos, George ; Gładysz-Dziaduś, Ewa ; Grebieszkow, Katarzyna ; Hegyi, Sándor ; Hohne, Claudia ; Kadija, Krešo ; Karev, Alexandre ; Kliemant, Michael ; Kniege, Stefan ; Kolesnikov, Vadim I. ; Kollegger, Thorsten ; Kornas, Ewelina ; Korus, Robert ; Kowalski, Marek ; Kraus, Ingrid ; Kreps, Michal ; Leeuwen, Marco van ; Lévai, Péter ; Litov, Leandr ; Lungwitz, Benjamin ; Makariev, Martin Vasilev ; Malakhov, Aleksandr I. ; Markert, Christina ; Mateev, Matej D. ; Mayes, Bill W. ; Melkumov, Georgy L. ; Meurer, Christine ; Mischke, André ; Mitrovski, Michael Kosta ; Molnar, József ; Mrowczynski, Stanislaw ; Pálla, Gabriella ; Panagiotou, Apostolos D. ; Panayotov, Dobromir ; Petridis, Athanasios ; Pikna, Miroslav ; Pinsky, Lawrence S. ; Puhlhofer, Falk ; Reid, Jeffrey G. ; Renfordt, Rainer Arno Ernst ; Richard, Agnes Carol Joanna ; Roland, Christof ; Roland, Gunther ; Rybczyński, Maciej ; Rybicki, Andrzej ; Sandoval, Andres ; Sann, Hans ; Schmitz, Norbert ; Seyboth, Peter ; Sikler, Ferenc ; Sitar, Branislav ; Skrzypczak, Ewa ; Stefanek, Grzegorz ; Stock, Reinhard ; Ströbele, Herbert ; Šuša, Tatjana ; Szentpetery, Imre ; Sziklai, János ; Trainor, Thomas A. ; Trubnikov, Victor ; Varga, Dezsö ; Vassiliou, Maria ; Veres, Gábor I. ; Vesztergombi, György ; Vranić, Danilo ; Wetzler, Alexander Albert ; Włodarczyk, Zbigniew ; Yoo, In-Kwon ; Zaranek, Jacek ; Zimanyi, József
The hadronic final state of central Pb+Pb collisions at 20, 30, 40, 80, and 158 AGeV has been measured by the CERN NA49 collaboration. The mean transverse mass of pions and kaons at midrapidity stays nearly constant in this energy range, whereas at lower energies, at the AGS, a steep increase with beam energy was measured. Compared to p+p collisions as well as to model calculations, anomalies in the energy dependence of pion and kaon production at lower SPS energies are observed. These findings can be explained, assuming that the energy density reached in central A+A collisions at lower SPS energies is sufficient to force the hot and dense nuclear matter into a deconfined phase.
Gröschel, Stefan ; Hübschmann, Daniel ; Raimondi, Francesco ; Horak, Peter ; Warsow, Gregor ; Fröhlich, Martina ; Klink, Barbara ; Gieldon, Laura ; Hutter, Barbara ; Kleinheinz, Kortine ; Bonekamp, David ; Marschal, Oliver ; Chudasama, Priya ; Mika, Jagoda ; Groth, Marie ; Uhrig, Sebastian ; Krämer, Stephen ; Heining, Christoph ; Heilig, Christoph E. ; Richter, Daniela ; Reisinger, Eva ; Pfütze, Katrin ; Eils, Roland ; Wolf, Stephan ; Kalle, Christof von ; Brandts, Christian Hubertus ; Scholl, Claudia ; Weichert, Wilko ; Richter, Stephan ; Bauer, Sebastian ; Penzel, Roland ; Schröck, Evelin ; Stenzinger, Albrecht ; Schlenk, Richard Friedrich ; Brors, Benedikt ; Russell, Robert B. ; Glimm, Hanno ; Schlesner, Matthias ; Fröhling, Stefan
Chordomas are rare bone tumors with few therapeutic options. Here we show, using whole-exome and genome sequencing within a precision oncology program, that advanced chordomas (n = 11) may be characterized by genomic patterns indicative of defective homologous recombination (HR) DNA repair and alterations affecting HR-related genes, including, for example, deletions and pathogenic germline variants of BRCA2, NBN, and CHEK2. A mutational signature associated with HR deficiency was significantly enriched in 72.7% of samples and co-occurred with genomic instability. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, which is preferentially toxic to HR-incompetent cells, led to prolonged clinical benefit in a patient with refractory chordoma, and whole-genome analysis at progression revealed a PARP1 p.T910A mutation predicted to disrupt the autoinhibitory PARP1 helical domain. These findings uncover a therapeutic opportunity in chordoma that warrants further exploration, and provide insight into the mechanisms underlying PARP inhibitor resistance.