TY  - JOUR
AU  - Kool, Marcel
AU  - Jones, David
AU  - Jäger, Natalie
AU  - Northcott, Paul A
AU  - Pugh, Trevor J
AU  - Hovestadt, Volker
AU  - Piro, Rosario M
AU  - Esparza, L Adriana
AU  - Markant, Shirley L
AU  - Remke, Marc
AU  - Milde, Till
AU  - Bourdeaut, Franck
AU  - Ryzhova, Marina
AU  - Sturm, Dominik
AU  - Pfaff, Elke
AU  - Stark, Sebastian
AU  - Hutter, Sonja
AU  - Seker-Cin, Huriye
AU  - Johann, Pascal
AU  - Bender, Sebastian
AU  - Schmidt, Christin
AU  - Rausch, Tobias
AU  - Shih, David
AU  - Reimand, Jüri
AU  - Sieber, Laura
AU  - Wittmann, Andrea
AU  - Linke, Linda
AU  - Witt, Hendrik
AU  - Weber, Ursula
AU  - Zapatka, Marc
AU  - König, Rainer
AU  - Beroukhim, Rameen
AU  - Bergthold, Guillaume
AU  - van Sluis, Peter
AU  - Volckmann, Richard
AU  - Koster, Jan
AU  - Versteeg, Rogier
AU  - Schmidt, Sabine
AU  - Wolf, Stephan
AU  - Lawerenz, Christian
AU  - Bartholomae, Cynthia C
AU  - von Kalle, Christof
AU  - Unterberg, Andreas
AU  - Herold-Mende, Christel
AU  - Hofer, Silvia
AU  - Kulozik, Andreas E
AU  - von Deimling, Andreas
AU  - Scheurlen, Wolfram
AU  - Felsberg, Jörg
AU  - Reifenberger, Guido
AU  - Hasselblatt, Martin
AU  - Crawford, John R
AU  - Grant, Gerald A
AU  - Jabado, Nada
AU  - Perry, Arie
AU  - Cowdrey, Cynthia
AU  - Croul, Sydney
AU  - Zadeh, Gelareh
AU  - Korbel, Jan O
AU  - Doz, Francois
AU  - Delattre, Olivier
AU  - Bader, Gary D
AU  - McCabe, Martin G
AU  - Collins, V Peter
AU  - Kieran, Mark W
AU  - Cho, Yoon-Jae
AU  - Pomeroy, Scott L
AU  - Witt, Olaf
AU  - Brors, Benedikt
AU  - Taylor, Michael D
AU  - Schüller, Ulrich
AU  - Korshunov, Andrey
AU  - Eils, Roland
AU  - Wechsler-Reya, Robert J
AU  - Lichter, Peter
AU  - Pfister, Stefan
TI  - Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.
JO  - Cancer cell
VL  - 25
IS  - 3
SN  - 1535-6108
CY  - Cambridge, Mass.
PB  - Cell Press
M1  - DKFZ-2017-03664
SP  - 393 - 405
PY  - 2014
AB  - Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.
KW  - Biphenyl Compounds (NLM Chemicals)
KW  - GLI2 protein, human (NLM Chemicals)
KW  - Hedgehog Proteins (NLM Chemicals)
KW  - Kruppel-Like Transcription Factors (NLM Chemicals)
KW  - LDE225 (NLM Chemicals)
KW  - MYCN protein, human (NLM Chemicals)
KW  - N-Myc Proto-Oncogene Protein (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
KW  - Oncogene Proteins (NLM Chemicals)
KW  - PTCH protein, human (NLM Chemicals)
KW  - Patched Receptors (NLM Chemicals)
KW  - Patched-1 Receptor (NLM Chemicals)
KW  - Ptch1 protein, mouse (NLM Chemicals)
KW  - Pyridines (NLM Chemicals)
KW  - Receptors, Cell Surface (NLM Chemicals)
KW  - Receptors, G-Protein-Coupled (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - SHH protein, human (NLM Chemicals)
KW  - SMO protein, human (NLM Chemicals)
KW  - SUFU protein, human (NLM Chemicals)
KW  - Smoothened Receptor (NLM Chemicals)
KW  - TP53 protein, human (NLM Chemicals)
KW  - Tumor Suppressor Protein p53 (NLM Chemicals)
KW  - Phosphatidylinositol 3-Kinases (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-akt (NLM Chemicals)
KW  - TERT protein, human (NLM Chemicals)
KW  - Telomerase (NLM Chemicals)
KW  - DDX3X protein, human (NLM Chemicals)
KW  - DEAD-box RNA Helicases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24651015
C2  - pmc:PMC4493053
DO  - DOI:10.1016/j.ccr.2014.02.004
UR  - https://inrepo02.dkfz.de/record/127641
ER  -