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Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition

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Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. / Kool, Marcel; Jones, David T W; Jäger, Natalie; Northcott, Paul A; Pugh, Trevor J; Hovestadt, Volker; Piro, Rosario M; Esparza, Lourdes Adriana; Markant, Shirley L; Remke, Marc; Milde, Till; Bourdeaut, Franck; Ryzhova, Marina; Sturm, Dominik; Pfaff, Elke; Stark, Sebastian; Hutter, Sonja; Seker-Cin, Huriye; Johann, Pascal-David; Bender, Sebastian; Schmidt, Christin; Rausch, Tobias; Shih, David; Reimand, Jüri; Sieber, Laura; Wittmann, Andrea; Linke, Linda; Witt, Hendrik; Weber, Ursula D; Zapatka, Marc; König, Rainer; Beroukhim, Rameen; Bergthold, Guillaume; van Sluis, Peter; Volckmann, Richard; Koster, Jan; Versteeg, Rogier; Schmidt, Sabine; Wolf, Stephan; Lawerenz, Chris; Bartholomae, Cynthia C; von Kalle, Christof; Unterberg, Andreas; Herold-Mende, Christel; Hofer, Silvia; Kulozik, Andreas E; Deimling, Andreas; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Hasselblatt, Martin; Crawford, John R; Grant, Gerald A; Jabado, Nada; Perry, Arie; Cowdrey, Cynthia J; Croul, Sydney; Zadeh, Gelareh; Korbel, Jan O; Doz, Francois; Delattre, Olivier; Bader, Gary D; McCabe, Martin G; Collins, V Peter; Kieran, Mark W; Cho, Yoon-Jae; Pomeroy, Scott L; Witt, Olaf; Brors, Benedikt; Taylor, Michael D; Schüller, Ulrich; Korshunov, Andrey; Eils, Roland; Wechsler-Reya, Robert J; Lichter, Peter; Pfister, Stefan M; ICGC PedBrain Tumor Project.

in: CANCER CELL, Jahrgang 25, Nr. 3, 17.03.2014, S. 393-405.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kool, M, Jones, DTW, Jäger, N, Northcott, PA, Pugh, TJ, Hovestadt, V, Piro, RM, Esparza, LA, Markant, SL, Remke, M, Milde, T, Bourdeaut, F, Ryzhova, M, Sturm, D, Pfaff, E, Stark, S, Hutter, S, Seker-Cin, H, Johann, P-D, Bender, S, Schmidt, C, Rausch, T, Shih, D, Reimand, J, Sieber, L, Wittmann, A, Linke, L, Witt, H, Weber, UD, Zapatka, M, König, R, Beroukhim, R, Bergthold, G, van Sluis, P, Volckmann, R, Koster, J, Versteeg, R, Schmidt, S, Wolf, S, Lawerenz, C, Bartholomae, CC, von Kalle, C, Unterberg, A, Herold-Mende, C, Hofer, S, Kulozik, AE, Deimling, A, Scheurlen, W, Felsberg, J, Reifenberger, G, Hasselblatt, M, Crawford, JR, Grant, GA, Jabado, N, Perry, A, Cowdrey, CJ, Croul, S, Zadeh, G, Korbel, JO, Doz, F, Delattre, O, Bader, GD, McCabe, MG, Collins, VP, Kieran, MW, Cho, Y-J, Pomeroy, SL, Witt, O, Brors, B, Taylor, MD, Schüller, U, Korshunov, A, Eils, R, Wechsler-Reya, RJ, Lichter, P, Pfister, SM & ICGC PedBrain Tumor Project 2014, 'Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition', CANCER CELL, Jg. 25, Nr. 3, S. 393-405. https://doi.org/10.1016/j.ccr.2014.02.004

APA

Kool, M., Jones, D. T. W., Jäger, N., Northcott, P. A., Pugh, T. J., Hovestadt, V., Piro, R. M., Esparza, L. A., Markant, S. L., Remke, M., Milde, T., Bourdeaut, F., Ryzhova, M., Sturm, D., Pfaff, E., Stark, S., Hutter, S., Seker-Cin, H., Johann, P-D., ... ICGC PedBrain Tumor Project (2014). Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. CANCER CELL, 25(3), 393-405. https://doi.org/10.1016/j.ccr.2014.02.004

Vancouver

Kool M, Jones DTW, Jäger N, Northcott PA, Pugh TJ, Hovestadt V et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. CANCER CELL. 2014 Mär 17;25(3):393-405. https://doi.org/10.1016/j.ccr.2014.02.004

Bibtex

@article{5f269f1905594b6bafd80153f966240b,
title = "Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition",
abstract = "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.",
keywords = "Adolescent, Adult, Animals, Base Sequence, Biphenyl Compounds, Cerebellar Neoplasms, Child, Child, Preschool, DEAD-box RNA Helicases, DNA Copy Number Variations, Drug Resistance, Neoplasm, Female, Gene Expression Profiling, Hedgehog Proteins, High-Throughput Nucleotide Sequencing, Humans, Infant, Kruppel-Like Transcription Factors, Male, Medulloblastoma, Mice, Mice, Inbred NOD, Mice, SCID, Molecular Sequence Data, N-Myc Proto-Oncogene Protein, Neoplasm Transplantation, Nuclear Proteins, Oncogene Proteins, Patched Receptors, Patched-1 Receptor, Phosphatidylinositol 3-Kinases, Promoter Regions, Genetic, Proto-Oncogene Proteins c-akt, Pyridines, Receptors, Cell Surface, Receptors, G-Protein-Coupled, Repressor Proteins, Signal Transduction, Smoothened Receptor, Telomerase, Tumor Suppressor Protein p53, Young Adult, Journal Article, Research Support, Non-U.S. Gov't",
author = "Marcel Kool and Jones, {David T W} and Natalie J{\"a}ger and Northcott, {Paul A} and Pugh, {Trevor J} and Volker Hovestadt and Piro, {Rosario M} and Esparza, {Lourdes Adriana} and Markant, {Shirley L} and Marc Remke and Till Milde and Franck Bourdeaut and Marina Ryzhova and Dominik Sturm and Elke Pfaff and Sebastian Stark and Sonja Hutter and Huriye Seker-Cin and Pascal-David Johann and Sebastian Bender and Christin Schmidt and Tobias Rausch and David Shih and J{\"u}ri Reimand and Laura Sieber and Andrea Wittmann and Linda Linke and Hendrik Witt and Weber, {Ursula D} and Marc Zapatka and Rainer K{\"o}nig and Rameen Beroukhim and Guillaume Bergthold and {van Sluis}, Peter and Richard Volckmann and Jan Koster and Rogier Versteeg and Sabine Schmidt and Stephan Wolf and Chris Lawerenz and Bartholomae, {Cynthia C} and {von Kalle}, Christof and Andreas Unterberg and Christel Herold-Mende and Silvia Hofer and Kulozik, {Andreas E} and Andreas Deimling and Wolfram Scheurlen and J{\"o}rg Felsberg and Guido Reifenberger and Martin Hasselblatt and Crawford, {John R} and Grant, {Gerald A} and Nada Jabado and Arie Perry and Cowdrey, {Cynthia J} and Sydney Croul and Gelareh Zadeh and Korbel, {Jan O} and Francois Doz and Olivier Delattre and Bader, {Gary D} and McCabe, {Martin G} and Collins, {V Peter} and Kieran, {Mark W} and Yoon-Jae Cho and Pomeroy, {Scott L} and Olaf Witt and Benedikt Brors and Taylor, {Michael D} and Ulrich Sch{\"u}ller and Andrey Korshunov and Roland Eils and Wechsler-Reya, {Robert J} and Peter Lichter and Pfister, {Stefan M} and {ICGC PedBrain Tumor Project}",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = mar,
day = "17",
doi = "10.1016/j.ccr.2014.02.004",
language = "English",
volume = "25",
pages = "393--405",
journal = "CANCER CELL",
issn = "1535-6108",
publisher = "Cell Press",
number = "3",

}

RIS

TY - JOUR

T1 - Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition

AU - Kool, Marcel

AU - Jones, David T W

AU - Jäger, Natalie

AU - Northcott, Paul A

AU - Pugh, Trevor J

AU - Hovestadt, Volker

AU - Piro, Rosario M

AU - Esparza, Lourdes 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-David

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 D

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, Chris

AU - Bartholomae, Cynthia C

AU - von Kalle, Christof

AU - Unterberg, Andreas

AU - Herold-Mende, Christel

AU - Hofer, Silvia

AU - Kulozik, Andreas E

AU - 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 J

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 M

AU - ICGC PedBrain Tumor Project

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/3/17

Y1 - 2014/3/17

N2 - 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.

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 - Adolescent

KW - Adult

KW - Animals

KW - Base Sequence

KW - Biphenyl Compounds

KW - Cerebellar Neoplasms

KW - Child

KW - Child, Preschool

KW - DEAD-box RNA Helicases

KW - DNA Copy Number Variations

KW - Drug Resistance, Neoplasm

KW - Female

KW - Gene Expression Profiling

KW - Hedgehog Proteins

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Infant

KW - Kruppel-Like Transcription Factors

KW - Male

KW - Medulloblastoma

KW - Mice

KW - Mice, Inbred NOD

KW - Mice, SCID

KW - Molecular Sequence Data

KW - N-Myc Proto-Oncogene Protein

KW - Neoplasm Transplantation

KW - Nuclear Proteins

KW - Oncogene Proteins

KW - Patched Receptors

KW - Patched-1 Receptor

KW - Phosphatidylinositol 3-Kinases

KW - Promoter Regions, Genetic

KW - Proto-Oncogene Proteins c-akt

KW - Pyridines

KW - Receptors, Cell Surface

KW - Receptors, G-Protein-Coupled

KW - Repressor Proteins

KW - Signal Transduction

KW - Smoothened Receptor

KW - Telomerase

KW - Tumor Suppressor Protein p53

KW - Young Adult

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ccr.2014.02.004

DO - 10.1016/j.ccr.2014.02.004

M3 - SCORING: Journal article

C2 - 24651015

VL - 25

SP - 393

EP - 405

JO - CANCER CELL

JF - CANCER CELL

SN - 1535-6108

IS - 3

ER -