Title: Preclinical Efficacy of the Mdm2 Inhibitor Rg7112 in Mdm2 Amplified and Significance Statement

Title: Preclinical efficacy of the MDM2 inhibitor RG7112 in MDM2 amplified and TP53 wild-type glioblastomas Authors: Maite Verreault, Charlotte Schmitt, Lauriane Goldwirt, Kristine Pelton, Samer Haidar, Camille Levasseur, Jeremy Guehennec, David Knoff, Marianne Labussiere, Yannick Marie, Azra H. Ligon, Karima Mokhtari, Khe Hoang-Xuan, Marc Sanson, Brian M Alexander, Patrick Y. Wen, Jean-Yves Delattre, Keith L. Ligon, Ahmed Idbaih Affiliations: 1: Inserm, U 1127, F-75013, Paris, France ; 2: CNRS, UMR 7225, F75013, Paris, France ; 3: Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, F-75013, Paris, France ; 4: Institut du Cerveau et de la Moëlle épinière, ICM, 47, Bd de l’Hôpital, F-75013, Paris, France ; 5: AP-HP, Hôpital universitaire Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, 47, Bd de l’Hopital, F-75013, Paris, France; 6: APHP, Hôpital de la Pitié-Salpêtrière, Service de Neuropathologie R Escourolle, 47, Bd de l’Hopital, F-75013, Paris, France; 7: OncoNeuroThèque biobank, Institut du Cerveau et de la Moëlle épinière, ICM, 47, Bd de l’Hopital, F-75013, Paris, France; 8: Department of Medical Oncology, Center for Molecular Oncologic Pathology, DanaFarber Cancer Institute, 450 Brookline Ave, MA, Boston, Massachusetts, USA, 02115; 9: Department of Pathology, Brigham and Women's Hospital, 75, Francis Street, Boston, MA, USA, 02115; 10: Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, MA, USA, 02115; 11: Institut du Cerveau et de la Moëlle épinière, Centre de neuroimagerie de recherche, CHU Pitié-Salpêtrière, 47, Bd de l’Hopital, 75013, Paris, France; 12: Laboratoire de Pharmacologie Biologique, Hôpital Saint-Louis, 1, avenue Claude-Vellefaux, 75010, Paris, France; 13: Department of Radiation Oncology, Dana-Farber/Brigham and Women’s Cancer Center, Harvard Medical School, 25 Shattuck Street, Boston, MA, USA, 02115; 14: Boston Children's Hospital, 300, Longwood avenue, Boston, MA 02115; 15: Department of Neurology, Brigham and Women’s Hospital Boston, 75, Francis Street, Boston, MA, USA, 02115; *, co-principal investigators Running title: Highly selective activity of RG7112 in glioblastoma