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 David Johann; Felix Sahm; Jüri Reimand; Alan sim 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 David Johann, Felix SahmJüri Reimand, Alan sim 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

IKM

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

713 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	164
Udgave nummer	5
Sider (fra-til)	1060-72
Antal sider	13
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2016.01.015
Status	Udgivet - 2016

Adgang til dokumentet

10.1016/j.cell.2016.01.015Licens: Andet

Citationsformater

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), 1060-72. 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 David; Sahm, Felix; Reimand, Jüri; Mackay, Alan sim; 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.

I: Cell, Bind 164, Nr. 5, 2016, s. 1060-72.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, AS, 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, C-M, 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, bind 164, nr. 5, s. 1060-72. 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 David ; Sahm, Felix ; Reimand, Jüri ; Mackay, Alan sim ; 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. I: Cell. 2016 ; Bind 164, Nr. 5. s. 1060-72.

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

abstract = "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.",

keywords = "Amino Acid Sequence, Central Nervous System Neoplasms, Child, DNA Methylation, Forkhead Transcription Factors, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Molecular Sequence Data, Neuroectodermal Tumors, Proto-Oncogene Proteins, Repressor Proteins, Signal Transduction, Tumor Suppressor Proteins, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

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 David} and Felix Sahm and J{\"u}ri Reimand and Mackay, {Alan sim} 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}ssler 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 Camelia-Maria Monoranu 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",

year = "2016",

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

language = "English",

volume = "164",

pages = "1060--72",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

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 David

AU - Sahm, Felix

AU - Reimand, Jüri

AU - Mackay, Alan sim

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

Y1 - 2016

N2 - 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 - 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.

KW - Amino Acid Sequence

KW - Central Nervous System Neoplasms

KW - Child

KW - DNA Methylation

KW - Forkhead Transcription Factors

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Molecular Sequence Data

KW - Neuroectodermal Tumors

KW - Proto-Oncogene Proteins

KW - Repressor Proteins

KW - Signal Transduction

KW - Tumor Suppressor Proteins

KW - Journal Article

KW - Research Support, N.I.H., Extramural

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

U2 - 10.1016/j.cell.2016.01.015

DO - 10.1016/j.cell.2016.01.015

M3 - Journal article

C2 - 26919435

VL - 164

SP - 1060

EP - 1072

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -