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

Research output: Contribution to journalArticle

232 Citations (Scopus)

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 languageEnglish
Pages (from-to)1060-1072
Number of pages13
JournalCell
Volume164
Issue number5
DOIs
Publication statusPublished - Feb 25 2016

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Primitive Neuroectodermal Tumors
Brain Neoplasms
Tumors
Brain
Neuroepithelial Neoplasms
Neoplasms
Nervous System Neoplasms
Ewing's Sarcoma
Neuroblastoma
Central Nervous System
Clinical Trials
Neurology
Therapeutics
Chemical activation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sturm, D., Orr, B. A., Toprak, U. H., Hovestadt, V., Jones, D. T. W., Capper, 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

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

In: Cell, Vol. 164, No. 5, 25.02.2016, p. 1060-1072.

Research output: Contribution to journalArticle

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
Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D et al. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell. 2016 Feb 25;164(5):1060-1072. https://doi.org/10.1016/j.cell.2016.01.015
Sturm, Dominik ; Orr, Brent A. ; Toprak, Umut H. ; Hovestadt, Volker ; Jones, David T W ; Capper, David ; Sill, Martin ; Buchhalter, Ivo ; Northcott, Paul A. ; Leis, Irina ; Ryzhova, Marina ; Koelsche, Christian ; Pfaff, Elke ; Allen, Sariah J. ; Balasubramanian, Gnanaprakash ; Worst, Barbara C. ; Pajtler, Kristian W. ; Brabetz, Sebastian ; Johann, Pascal D. ; Sahm, Felix ; Reimand, Jüri ; Mackay, Alan ; Carvalho, Diana M. ; Remke, Marc ; Phillips, Joanna J. ; Perry, Arie ; Cowdrey, Cynthia ; Drissi, Rachid ; Fouladi, Maryam ; Giangaspero, Felice ; Łastowska, Maria ; Grajkowska, Wiesława ; Scheurlen, Wolfram ; Pietsch, Torsten ; Hagel, Christian ; Gojo, Johannes ; Lötsch, Daniela ; Berger, Walter ; Slavc, Irene ; Haberler, Christine ; Jouvet, Anne ; Holm, Stefan ; Hofer, Silvia ; Prinz, Marco ; Keohane, Catherine ; Fried, Iris ; Mawrin, Christian ; Scheie, David ; Mobley, Bret C. ; Schniederjan, Matthew J. ; Santi, Mariarita ; Buccoliero, Anna M. ; Dahiya, Sonika ; Kramm, Christof M. ; Von Bueren, André O. ; Von Hoff, Katja ; Rutkowski, Stefan ; Herold-Mende, Christel ; Frühwald, Michael C. ; Milde, Till ; Hasselblatt, Martin ; Wesseling, Pieter ; Rößler, Jochen ; Schüller, Ulrich ; Ebinger, Martin ; Schittenhelm, Jens ; Frank, Stephan ; Grobholz, Rainer ; Vajtai, Istvan ; Hans, Volkmar ; Schneppenheim, Reinhard ; Zitterbart, Karel ; Collins, V. Peter ; Aronica, Eleonora ; Varlet, Pascale ; Puget, Stephanie ; Dufour, Christelle ; Grill, Jacques ; Figarella-Branger, Dominique ; Wolter, Marietta ; Schuhmann, Martin U. ; Shalaby, Tarek ; Grotzer, Michael ; Van Meter, Timothy ; Monoranu, Camelia Maria ; Felsberg, Jörg ; Reifenberger, Guido ; Snuderl, Matija ; Forrester, Lynn Ann ; Koster, Jan ; Versteeg, Rogier ; Volckmann, Richard ; Van Sluis, Peter ; Wolf, Stephan ; Mikkelsen, Tom ; Gajjar, Amar ; Aldape, Kenneth ; Moore, Andrew S. ; Taylor, Michael D. ; Jones, Chris ; Jabado, Nada ; Karajannis, Matthias A. ; Eils, Roland ; Schlesner, Matthias ; Lichter, Peter ; Von Deimling, Andreas ; Pfister, Stefan M. ; Ellison, David W. ; Korshunov, Andrey ; Kool, Marcel. / New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. In: Cell. 2016 ; Vol. 164, No. 5. pp. 1060-1072.
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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.",
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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.

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