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

D. Sturm; B.A. Orr; U.H. Toprak; V. Hovestadt; D.T.W. Jones; D. Capper; M. Sill; I. Buchhalter; P.A. Northcott; I. Leis; M. Ryzhova; C. Koelsche; E. Pfaff; S.J. Allen; G. Balasubramanian; B.C. Worst; K.W. Pajtler; S. Brabetz; P.D. Johann; F. Sahm; J. Reimand; A. Mackay; D.M. Carvalho; M. Remke; J.J. Phillips; A. Perry; C. Cowdrey; R. Drissi; M. Fouladi; F. Giangaspero; M. Łastowska; W. Grajkowska; W. Scheurlen; T. Pietsch; C. Hagel; J. Gojo; D. Lötsch; W. Berger; I. Slavc; C. Haberler; A. Jouvet; S. Holm; S. Hofer; M. Prinz; C. Keohane; I. Fried; C. Mawrin; D. Scheie; B.C. Mobley; M.J. Schniederjan; M. Santi; A.M. Buccoliero; S. Dahiya; C.M. Kramm; A.O. von Bueren; K. von Hoff; S. Rutkowski; C. Herold-Mende; M.C. Frühwald; T. Milde; M. Hasselblatt; P. Wesseling; J. Rößler; U. Schüller; M. Ebinger; J. Schittenhelm; S. Frank; R. Grobholz; I. Vajtai; V. Hans; R. Schneppenheim; K. Zitterbart; V.P. Collins; E. Aronica; P. Varlet; S. Puget; C. Dufour; J. Grill; D. Figarella-Branger; M. Wolter; M.U. Schuhmann; T. Shalaby; M. Grotzer; T. van Meter; C.M. Monoranu; J. Felsberg; G. Reifenberger; M. Snuderl; L.A. Forrester; J. Koster; R. Versteeg; R. Volckmann; P. van Sluis; S. Wolf; T. Mikkelsen; A. Gajjar; K. Aldape; A.S. Moore; M.D. Taylor; C. Jones; N. Jabado; M.A. Karajannis; R. Eils; M. Schlesner; P. Lichter; A. von Deimling; S.M. Pfister; D.W. Ellison; A. Korshunov; M. Kool; Maria Lastowska; Michael C. Fruehwald; Ulrich Schueller

doi:https://doi.org/10.1016/j.cell.2016.01.015

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

D. Sturm, B.A. Orr, U.H. Toprak, V. Hovestadt, D.T.W. Jones, D. Capper, M. Sill, I. Buchhalter, P.A. Northcott, I. Leis, M. Ryzhova, C. Koelsche, E. Pfaff, S.J. Allen, G. Balasubramanian, B.C. Worst, K.W. Pajtler, S. Brabetz, P.D. Johann, F. SahmJ. Reimand, A. Mackay, D.M. Carvalho, M. Remke, J.J. Phillips, A. Perry, C. Cowdrey, R. Drissi, M. Fouladi, F. Giangaspero, M. Łastowska, W. Grajkowska, W. Scheurlen, T. Pietsch, C. Hagel, J. Gojo, D. Lötsch, W. Berger, I. Slavc, C. Haberler, A. Jouvet, S. Holm, S. Hofer, M. Prinz, C. Keohane, I. Fried, C. Mawrin, D. Scheie, B.C. Mobley, M.J. Schniederjan, M. Santi, A.M. Buccoliero, S. Dahiya, C.M. Kramm, A.O. von Bueren, K. von Hoff, S. Rutkowski, C. Herold-Mende, M.C. Frühwald, T. Milde, M. Hasselblatt, P. Wesseling, J. Rößler, U. Schüller, M. Ebinger, J. Schittenhelm, S. Frank, R. Grobholz, I. Vajtai, V. Hans, R. Schneppenheim, K. Zitterbart, V.P. Collins, E. Aronica, P. Varlet, S. Puget, C. Dufour, J. Grill, D. Figarella-Branger, M. Wolter, M.U. Schuhmann, T. Shalaby, M. Grotzer, T. van Meter, C.M. Monoranu, J. Felsberg, G. Reifenberger, M. Snuderl, L.A. Forrester, J. Koster, R. Versteeg, R. Volckmann, P. van Sluis, S. Wolf, T. Mikkelsen, A. Gajjar, K. Aldape, A.S. Moore, M.D. Taylor, C. Jones, N. Jabado, M.A. Karajannis, R. Eils, M. Schlesner, P. Lichter, A. von Deimling, S.M. Pfister, D.W. Ellison, A. Korshunov, M. Kool, Maria Lastowska, Michael C. Fruehwald, Ulrich Schueller

Research output: Contribution to journal › Article › Academic › peer-review

625 Citations (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.

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

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https://doi.org/10.1016/j.cell.2016.01.015

https://pure.uva.nl/ws/files/2720985/175060_New_Brain_Tumor_Entities_Emerge.pdf

Cite this

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., ... Schueller, U. (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{93b8f0f0bece4af1b9124dd3d46306fa,

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.",

author = "D. Sturm and B.A. Orr and U.H. Toprak and V. Hovestadt and D.T.W. Jones and D. Capper and M. Sill and I. Buchhalter and P.A. Northcott and I. Leis and M. Ryzhova and C. Koelsche and E. Pfaff and S.J. Allen and G. Balasubramanian and B.C. Worst and K.W. Pajtler and S. Brabetz and P.D. Johann and F. Sahm and J. Reimand and A. Mackay and D.M. Carvalho and M. Remke and J.J. Phillips and A. Perry and C. Cowdrey and R. Drissi and M. Fouladi and F. Giangaspero and M. {\L}astowska and W. Grajkowska and W. Scheurlen and T. Pietsch and C. Hagel and J. Gojo and D. L{\"o}tsch and W. Berger and I. Slavc and C. Haberler and A. Jouvet and S. Holm and S. Hofer and M. Prinz and C. Keohane and I. Fried and C. Mawrin and D. Scheie and B.C. Mobley and M.J. Schniederjan and M. Santi and A.M. Buccoliero and S. Dahiya and C.M. Kramm and {von Bueren}, A.O. and {von Hoff}, K. and S. Rutkowski and C. Herold-Mende and M.C. Fr{\"u}hwald and T. Milde and M. Hasselblatt and P. Wesseling and J. R{\"o}{\ss}ler and U. Sch{\"u}ller and M. Ebinger and J. Schittenhelm and S. Frank and R. Grobholz and I. Vajtai and V. Hans and R. Schneppenheim and K. Zitterbart and V.P. Collins and E. Aronica and P. Varlet and S. Puget and C. Dufour and J. Grill and D. Figarella-Branger and M. Wolter and M.U. Schuhmann and T. Shalaby and M. Grotzer and {van Meter}, T. and C.M. Monoranu and J. Felsberg and G. Reifenberger and M. Snuderl and L.A. Forrester and J. Koster and R. Versteeg and R. Volckmann and {van Sluis}, P. and S. Wolf and T. Mikkelsen and A. Gajjar and K. Aldape and A.S. Moore and M.D. Taylor and C. Jones and N. Jabado and M.A. Karajannis and R. Eils and M. Schlesner and P. Lichter and {von Deimling}, A. and S.M. Pfister and D.W. Ellison and A. Korshunov and M. Kool and Maria Lastowska and Fruehwald, {Michael C.} and Ulrich Schueller",

note = "With supplemental information",

year = "2016",

month = feb,

day = "25",

doi = "https://doi.org/10.1016/j.cell.2016.01.015",

language = "English",

volume = "164",

pages = "1060--1072",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

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, Lastowska, M, Fruehwald, MC & Schueller, U 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, D.

AU - Orr, B.A.

AU - Toprak, U.H.

AU - Hovestadt, V.

AU - Jones, D.T.W.

AU - Capper, D.

AU - Sill, M.

AU - Buchhalter, I.

AU - Northcott, P.A.

AU - Leis, I.

AU - Ryzhova, M.

AU - Koelsche, C.

AU - Pfaff, E.

AU - Allen, S.J.

AU - Balasubramanian, G.

AU - Worst, B.C.

AU - Pajtler, K.W.

AU - Brabetz, S.

AU - Johann, P.D.

AU - Sahm, F.

AU - Reimand, J.

AU - Mackay, A.

AU - Carvalho, D.M.

AU - Remke, M.

AU - Phillips, J.J.

AU - Perry, A.

AU - Cowdrey, C.

AU - Drissi, R.

AU - Fouladi, M.

AU - Giangaspero, F.

AU - Łastowska, M.

AU - Grajkowska, W.

AU - Scheurlen, W.

AU - Pietsch, T.

AU - Hagel, C.

AU - Gojo, J.

AU - Lötsch, D.

AU - Berger, W.

AU - Slavc, I.

AU - Haberler, C.

AU - Jouvet, A.

AU - Holm, S.

AU - Hofer, S.

AU - Prinz, M.

AU - Keohane, C.

AU - Fried, I.

AU - Mawrin, C.

AU - Scheie, D.

AU - Mobley, B.C.

AU - Schniederjan, M.J.

AU - Santi, M.

AU - Buccoliero, A.M.

AU - Dahiya, S.

AU - Kramm, C.M.

AU - von Bueren, A.O.

AU - von Hoff, K.

AU - Rutkowski, S.

AU - Herold-Mende, C.

AU - Frühwald, M.C.

AU - Milde, T.

AU - Hasselblatt, M.

AU - Wesseling, P.

AU - Rößler, J.

AU - Schüller, U.

AU - Ebinger, M.

AU - Schittenhelm, J.

AU - Frank, S.

AU - Grobholz, R.

AU - Vajtai, I.

AU - Hans, V.

AU - Schneppenheim, R.

AU - Zitterbart, K.

AU - Collins, V.P.

AU - Aronica, E.

AU - Varlet, P.

AU - Puget, S.

AU - Dufour, C.

AU - Grill, J.

AU - Figarella-Branger, D.

AU - Wolter, M.

AU - Schuhmann, M.U.

AU - Shalaby, T.

AU - Grotzer, M.

AU - van Meter, T.

AU - Monoranu, C.M.

AU - Felsberg, J.

AU - Reifenberger, G.

AU - Snuderl, M.

AU - Forrester, L.A.

AU - Koster, J.

AU - Versteeg, R.

AU - Volckmann, R.

AU - van Sluis, P.

AU - Wolf, S.

AU - Mikkelsen, T.

AU - Gajjar, A.

AU - Aldape, K.

AU - Moore, A.S.

AU - Taylor, M.D.

AU - Jones, C.

AU - Jabado, N.

AU - Karajannis, M.A.

AU - Eils, R.

AU - Schlesner, M.

AU - Lichter, P.

AU - von Deimling, A.

AU - Pfister, S.M.

AU - Ellison, D.W.

AU - Korshunov, A.

AU - Kool, M.

AU - Lastowska, Maria

AU - Fruehwald, Michael C.

AU - Schueller, Ulrich

N1 - With supplemental information

PY - 2016/2/25

Y1 - 2016/2/25

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.

U2 - https://doi.org/10.1016/j.cell.2016.01.015

DO - https://doi.org/10.1016/j.cell.2016.01.015

M3 - Article

C2 - 26919435

SN - 0092-8674

VL - 164

SP - 1060

EP - 1072

JO - Cell

JF - Cell

IS - 5

ER -