New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Dominik Sturm; Brent A. Orr; Umut H. Toprak; Volker Hovestadt; David T.W. Jones; David Capper; Martin Sill; Ivo Buchhalter; Paul A. Northcott; Irina Leis; Marina Ryzhova; Christian Koelsche; Elke Pfaff; Sariah J. Allen; Gnanaprakash Balasubramanian; Barbara C. Worst; Kristian W. Pajtler; Sebastian Brabetz; Pascal D. Johann; Felix Sahm; Jüri Reimand; Alan Mackay; Diana M. Carvalho; Marc Remke; Joanna J. Phillips; Arie Perry; Cynthia Cowdrey; Rachid Drissi; Maryam Fouladi; Felice Giangaspero; Maria Łastowska; Wiesława Grajkowska; Wolfram Scheurlen; Torsten Pietsch; Christian Hagel; Johannes Gojo; Daniela Lötsch; Walter Berger; Irene Slavc; Christine Haberler; Anne Jouvet; Stefan Holm; Silvia Hofer; Marco Prinz; Catherine Keohane; Iris Fried; Christian Mawrin; David Scheie; Bret C. Mobley; Matthew J. Schniederjan; Mariarita Santi; Anna M. Buccoliero; Sonika Dahiya; Christof M. Kramm; André O. Von Bueren; Katja Von Hoff; Stefan Rutkowski; Christel Herold-Mende; Michael C. Frühwald; Till Milde; Martin Hasselblatt; Pieter Wesseling; Jochen Rößler; Ulrich Schüller; Martin Ebinger; Jens Schittenhelm; Stephan Frank; Rainer Grobholz; Istvan Vajtai; Volkmar Hans; Reinhard Schneppenheim; Karel Zitterbart; V. Peter Collins; Eleonora Aronica; Pascale Varlet; Stephanie Puget; Christelle Dufour; Jacques Grill; Dominique Figarella-Branger; Marietta Wolter; Martin U. Schuhmann; Tarek Shalaby; Michael Grotzer; Timothy Van Meter; Camelia Maria Monoranu; Jörg Felsberg; Guido Reifenberger; Matija Snuderl; Lynn Ann Forrester; Jan Koster; Rogier Versteeg; Richard Volckmann; Peter Van Sluis; Stephan Wolf; Tom Mikkelsen; Amar Gajjar; Kenneth Aldape; Andrew S. Moore; Michael D. Taylor; Chris Jones; Nada Jabado; Matthias A. Karajannis; Roland Eils; Matthias Schlesner; Peter Lichter; Andreas Von Deimling; Stefan M. Pfister; David W. Ellison; Andrey Korshunov; Marcel Kool

doi:10.1016/j.cell.2016.01.015

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Dominik Sturm, Brent A. Orr, Umut H. Toprak, Volker Hovestadt, David T.W. Jones, David Capper, Martin Sill, Ivo Buchhalter, Paul A. Northcott, Irina Leis, Marina Ryzhova, Christian Koelsche, Elke Pfaff, Sariah J. Allen, Gnanaprakash Balasubramanian, Barbara C. Worst, Kristian W. Pajtler, Sebastian Brabetz, Pascal D. Johann, Felix SahmJüri Reimand, Alan Mackay, Diana M. Carvalho, Marc Remke, Joanna J. Phillips, Arie Perry, Cynthia Cowdrey, Rachid Drissi, Maryam Fouladi, Felice Giangaspero, Maria Łastowska, Wiesława Grajkowska, Wolfram Scheurlen, Torsten Pietsch, Christian Hagel, Johannes Gojo, Daniela Lötsch, Walter Berger, Irene Slavc, Christine Haberler, Anne Jouvet, Stefan Holm, Silvia Hofer, Marco Prinz, Catherine Keohane, Iris Fried, Christian Mawrin, David Scheie, Bret C. Mobley, Matthew J. Schniederjan, Mariarita Santi, Anna M. Buccoliero, Sonika Dahiya, Christof M. Kramm, André O. Von Bueren, Katja Von Hoff, Stefan Rutkowski, Christel Herold-Mende, Michael C. Frühwald, Till Milde, Martin Hasselblatt, Pieter Wesseling, Jochen Rößler, Ulrich Schüller, Martin Ebinger, Jens Schittenhelm, Stephan Frank, Rainer Grobholz, Istvan Vajtai, Volkmar Hans, Reinhard Schneppenheim, Karel Zitterbart, V. Peter Collins, Eleonora Aronica, Pascale Varlet, Stephanie Puget, Christelle Dufour, Jacques Grill, Dominique Figarella-Branger, Marietta Wolter, Martin U. Schuhmann, Tarek Shalaby, Michael Grotzer, Timothy Van Meter, Camelia Maria Monoranu, Jörg Felsberg, Guido Reifenberger, Matija Snuderl, Lynn Ann Forrester, Jan Koster, Rogier Versteeg, Richard Volckmann, Peter Van Sluis, Stephan Wolf, Tom Mikkelsen, Amar Gajjar, Kenneth Aldape, Andrew S. Moore, Michael D. Taylor, Chris Jones, Nada Jabado, Matthias A. Karajannis, Roland Eils, Matthias Schlesner, Peter Lichter, Andreas Von Deimling, Stefan M. Pfister, David W. Ellison, Andrey Korshunov, Marcel Kool

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Abstract

Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Original language	English
Pages (from-to)	1060-1072
Number of pages	13
Journal	Cell
Volume	164
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2016.01.015
State	Published - Feb 25 2016

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10.1016/j.cell.2016.01.015

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Sturm, D., Orr, B. A., Toprak, U. H., Hovestadt, V., Jones, D. T. W., Capper, D., Sill, M., Buchhalter, I., Northcott, P. A., Leis, I., Ryzhova, M., Koelsche, C., Pfaff, E., Allen, S. J., Balasubramanian, G., Worst, B. C., Pajtler, K. W., Brabetz, S., Johann, P. D., ... Kool, M. (2016). New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell, 164(5), 1060-1072. https://doi.org/10.1016/j.cell.2016.01.015

@article{30ee8fba3ee64301ac10059e00911957,

title = "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs",

abstract = "Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated {"}CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2),{"} {"}CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC),{"} {"}CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1),{"} and {"}CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR),{"} will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.",

author = "Dominik Sturm and Orr, {Brent A.} and Toprak, {Umut H.} and Volker Hovestadt and Jones, {David T.W.} and David Capper and Martin Sill and Ivo Buchhalter and Northcott, {Paul A.} and Irina Leis and Marina Ryzhova and Christian Koelsche and Elke Pfaff and Allen, {Sariah J.} and Gnanaprakash Balasubramanian and Worst, {Barbara C.} and Pajtler, {Kristian W.} and Sebastian Brabetz and Johann, {Pascal D.} and Felix Sahm and J{\"u}ri Reimand and Alan Mackay and Carvalho, {Diana M.} and Marc Remke and Phillips, {Joanna J.} and Arie Perry and Cynthia Cowdrey and Rachid Drissi and Maryam Fouladi and Felice Giangaspero and Maria {\L}astowska and Wies{\l}awa Grajkowska and Wolfram Scheurlen and Torsten Pietsch and Christian Hagel and Johannes Gojo and Daniela L{\"o}tsch and Walter Berger and Irene Slavc and Christine Haberler and Anne Jouvet and Stefan Holm and Silvia Hofer and Marco Prinz and Catherine Keohane and Iris Fried and Christian Mawrin and David Scheie and Mobley, {Bret C.} and Schniederjan, {Matthew J.} and Mariarita Santi and Buccoliero, {Anna M.} and Sonika Dahiya and Kramm, {Christof M.} and {Von Bueren}, {Andr{\'e} O.} and {Von Hoff}, Katja and Stefan Rutkowski and Christel Herold-Mende and Fr{\"u}hwald, {Michael C.} and Till Milde and Martin Hasselblatt and Pieter Wesseling and Jochen R{\"o}{\ss}ler and Ulrich Sch{\"u}ller and Martin Ebinger and Jens Schittenhelm and Stephan Frank and Rainer Grobholz and Istvan Vajtai and Volkmar Hans and Reinhard Schneppenheim and Karel Zitterbart and Collins, {V. Peter} and Eleonora Aronica and Pascale Varlet and Stephanie Puget and Christelle Dufour and Jacques Grill and Dominique Figarella-Branger and Marietta Wolter and Schuhmann, {Martin U.} and Tarek Shalaby and Michael Grotzer and {Van Meter}, Timothy and Monoranu, {Camelia Maria} and J{\"o}rg Felsberg and Guido Reifenberger and Matija Snuderl and Forrester, {Lynn Ann} and Jan Koster and Rogier Versteeg and Richard Volckmann and {Van Sluis}, Peter and Stephan Wolf and Tom Mikkelsen and Amar Gajjar and Kenneth Aldape and Moore, {Andrew S.} and Taylor, {Michael D.} and Chris Jones and Nada Jabado and Karajannis, {Matthias A.} and Roland Eils and Matthias Schlesner and Peter Lichter and {Von Deimling}, Andreas and Pfister, {Stefan M.} and Ellison, {David W.} and Andrey Korshunov and Marcel Kool",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = feb,

day = "25",

doi = "10.1016/j.cell.2016.01.015",

language = "English",

volume = "164",

pages = "1060--1072",

journal = "Cell",

issn = "0092-8674",

number = "5",

}

Sturm, D, Orr, BA, Toprak, UH, Hovestadt, V, Jones, DTW, Capper, D, Sill, M, Buchhalter, I, Northcott, PA, Leis, I, Ryzhova, M, Koelsche, C, Pfaff, E, Allen, SJ, Balasubramanian, G, Worst, BC, Pajtler, KW, Brabetz, S, Johann, PD, Sahm, F, Reimand, J, Mackay, A, Carvalho, DM, Remke, M, Phillips, JJ, Perry, A, Cowdrey, C, Drissi, R, Fouladi, M, Giangaspero, F, Łastowska, M, Grajkowska, W, Scheurlen, W, Pietsch, T, Hagel, C, Gojo, J, Lötsch, D, Berger, W, Slavc, I, Haberler, C, Jouvet, A, Holm, S, Hofer, S, Prinz, M, Keohane, C, Fried, I, Mawrin, C, Scheie, D, Mobley, BC, Schniederjan, MJ, Santi, M, Buccoliero, AM, Dahiya, S, Kramm, CM, Von Bueren, AO, Von Hoff, K, Rutkowski, S, Herold-Mende, C, Frühwald, MC, Milde, T, Hasselblatt, M, Wesseling, P, Rößler, J, Schüller, U, Ebinger, M, Schittenhelm, J, Frank, S, Grobholz, R, Vajtai, I, Hans, V, Schneppenheim, R, Zitterbart, K, Collins, VP, Aronica, E, Varlet, P, Puget, S, Dufour, C, Grill, J, Figarella-Branger, D, Wolter, M, Schuhmann, MU, Shalaby, T, Grotzer, M, Van Meter, T, Monoranu, CM, Felsberg, J, Reifenberger, G, Snuderl, M, Forrester, LA, Koster, J, Versteeg, R, Volckmann, R, Van Sluis, P, Wolf, S, Mikkelsen, T, Gajjar, A, Aldape, K, Moore, AS, Taylor, MD, Jones, C, Jabado, N, Karajannis, MA, Eils, R, Schlesner, M, Lichter, P, Von Deimling, A, Pfister, SM, Ellison, DW, Korshunov, A & Kool, M 2016, 'New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs', Cell, vol. 164, no. 5, pp. 1060-1072. https://doi.org/10.1016/j.cell.2016.01.015

TY - JOUR

T1 - New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

AU - Sturm, Dominik

AU - Orr, Brent A.

AU - Toprak, Umut H.

AU - Hovestadt, Volker

AU - Jones, David T.W.

AU - Capper, David

AU - Sill, Martin

AU - Buchhalter, Ivo

AU - Northcott, Paul A.

AU - Leis, Irina

AU - Ryzhova, Marina

AU - Koelsche, Christian

AU - Pfaff, Elke

AU - Allen, Sariah J.

AU - Balasubramanian, Gnanaprakash

AU - Worst, Barbara C.

AU - Pajtler, Kristian W.

AU - Brabetz, Sebastian

AU - Johann, Pascal D.

AU - Sahm, Felix

AU - Reimand, Jüri

AU - Mackay, Alan

AU - Carvalho, Diana M.

AU - Remke, Marc

AU - Phillips, Joanna J.

AU - Perry, Arie

AU - Cowdrey, Cynthia

AU - Drissi, Rachid

AU - Fouladi, Maryam

AU - Giangaspero, Felice

AU - Łastowska, Maria

AU - Grajkowska, Wiesława

AU - Scheurlen, Wolfram

AU - Pietsch, Torsten

AU - Hagel, Christian

AU - Gojo, Johannes

AU - Lötsch, Daniela

AU - Berger, Walter

AU - Slavc, Irene

AU - Haberler, Christine

AU - Jouvet, Anne

AU - Holm, Stefan

AU - Hofer, Silvia

AU - Prinz, Marco

AU - Keohane, Catherine

AU - Fried, Iris

AU - Mawrin, Christian

AU - Scheie, David

AU - Mobley, Bret C.

AU - Schniederjan, Matthew J.

AU - Santi, Mariarita

AU - Buccoliero, Anna M.

AU - Dahiya, Sonika

AU - Kramm, Christof M.

AU - Von Bueren, André O.

AU - Von Hoff, Katja

AU - Rutkowski, Stefan

AU - Herold-Mende, Christel

AU - Frühwald, Michael C.

AU - Milde, Till

AU - Hasselblatt, Martin

AU - Wesseling, Pieter

AU - Rößler, Jochen

AU - Schüller, Ulrich

AU - Ebinger, Martin

AU - Schittenhelm, Jens

AU - Frank, Stephan

AU - Grobholz, Rainer

AU - Vajtai, Istvan

AU - Hans, Volkmar

AU - Schneppenheim, Reinhard

AU - Zitterbart, Karel

AU - Collins, V. Peter

AU - Aronica, Eleonora

AU - Varlet, Pascale

AU - Puget, Stephanie

AU - Dufour, Christelle

AU - Grill, Jacques

AU - Figarella-Branger, Dominique

AU - Wolter, Marietta

AU - Schuhmann, Martin U.

AU - Shalaby, Tarek

AU - Grotzer, Michael

AU - Van Meter, Timothy

AU - Monoranu, Camelia Maria

AU - Felsberg, Jörg

AU - Reifenberger, Guido

AU - Snuderl, Matija

AU - Forrester, Lynn Ann

AU - Koster, Jan

AU - Versteeg, Rogier

AU - Volckmann, Richard

AU - Van Sluis, Peter

AU - Wolf, Stephan

AU - Mikkelsen, Tom

AU - Gajjar, Amar

AU - Aldape, Kenneth

AU - Moore, Andrew S.

AU - Taylor, Michael D.

AU - Jones, Chris

AU - Jabado, Nada

AU - Karajannis, Matthias A.

AU - Eils, Roland

AU - Schlesner, Matthias

AU - Lichter, Peter

AU - Von Deimling, Andreas

AU - Pfister, Stefan M.

AU - Ellison, David W.

AU - Korshunov, Andrey

AU - Kool, Marcel

PY - 2016/2/25

Y1 - 2016/2/25

N2 - Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

AB - Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

UR - http://www.scopus.com/inward/record.url?scp=84959433571&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2016.01.015

DO - 10.1016/j.cell.2016.01.015

M3 - Article

C2 - 26919435

AN - SCOPUS:84959433571

SN - 0092-8674

VL - 164

SP - 1060

EP - 1072

JO - Cell

JF - Cell

IS - 5

ER -

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

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