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

Dominik Sturm (1) , Brent A.Orr (2) , Umut H.Toprak (1) , Volker Hovestadt (1) , David T. W. Jones (1) , David Capper (3) , Martin Sill (1) , Ivo Buchhalter (1) , Paul A.Northcott (1) , Irina Leis (1) , Marina Ryzhova (1) , Christian Koelsche (4) , Elke Pfaff (1) , Sariah J.Allen (2) , Gnanaprakash Balasubramanian (1) , Barbara C. Worst (1) , Kristian W. Pajtler (1) , Sebastian Brabetz (1) , Pascal D. Johann (1) , Felix Sahm (1) , Jüri Reimand (5) , Alan Mackay (6) , Diana M. Carvalho (6) , Marc Remke (5) , Joanna J. Phillips (7) , Arie Perry (7) , Cynthia Cowdrey (7) , Rachid Drissi (8) , Maryam Fouladi (8) , Felice Giangaspero (9) , Maria Łastowska (10) , Wiesława Grajkowska (10) , Wolfram Scheurlen (11) , Torsten Pietsch (12) , Christian Hagel (13) , Johannes Gojo (14) , Daniela Lötsch (14) , Walter Berger (14) , Irene Slavc (14) , Christine Haberler (14) , Anne Jouvet (15) , Stefan Holm (16) , Silvia Hofer (17) , Marco Prinz (18) , Catherine Keohane (19) , Iris Fried (20) , Christian Mawrin (21) , David Scheie (22) , Bret C. Mobley (23) , Matthew J.Schniederjan (24) , Mariarita Santi (25) , Anna M. Buccoliero (26) , Sonika Dahiya (27) , Christof M. Kramm (28) , André O. von Bueren (28) , Katja von Hoff (13) , Stefan Rutkowski (13) , Christel Herold-Mende (1) , Michael C. Frühwald (29) , Till Milde (1) , Martin Hasselblatt (30) , Pieter Wesseling (31) , Jochen Rössler (32) , Ulrich Schüller (33) , Martin Ebinger (34) , Jens Schittenhelm (34) , Stephan Frank (35) , Rainer Grobholz (36) , Istvan Vajtai (37) , Volkmar Hans (38) , Reinhard Schneppenheim (13) , Karel Zitterbart (39) , Peter V. Collins (40) , Eleonora Aronica (41) , Pascale Varlet (42) , Jacques Grill (43, 44) , Stephanie Puget (45) , Christelle Dufour (44, 43) , Dominique Figarella-Branger (46) , Marietta Wolter (33) , Martin U. Schuhmann (33) , Tarek Shalaby (47) , Michael Grotzer (47) , Timothy van Meter (48) , Camelia-Maria Monoranu (49) , Jörg Felsberg (50) , Guido Reifenberger (50) , Matija Snuder (50) , Lynn Ann Forrester (51) , Jan Koster (41) , Rogier Versteeg (52) , Richard Volckmann (52) , Peter van Sluis (52) , Stephan Wolf (1) , Tom Mikkelsen (53) , Amar Gajjar (2) , Kenneth Aldape (54) , Andrew S. Moore (55) , Michael D. Taylor (5) , Chris Jones (6) , Nada Jabado (56) , Matthias A. Karajannis (51) , Roland Eils (1) , Matthias Schlesner (1) , Peter Lichter (1) , Andreas von Deimling (2) , Stefan M. Pfister (1) , David W. Ellison (2) , Andrey Korshunov (1) , Marcel Kool (1)

1 Heidelberg University Hospital [Heidelberg]
2 St Jude Children's Research Hospital
3 Department of Neuropathology
4 NNBNI - NN Burdenko Neurosurgical Institute
5 University of Toronto
6 The Institute of Cancer Research
7 UC San Francisco - University of California [San Francisco]
8 Children's Hospital Medical Center
9 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
10 The Children's Memorial Health Institute
11 Cnopf’sche Kinderklinik -
12 Universität Bonn = University of Bonn
13 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
14 Medizinische Universität Wien = Medical University of Vienna
15 Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
16 Karolinska Institutet [Stockholm]
17 Luzerner Kantonsspital
18 University of Freiburg [Freiburg]
19 Cork University Hospital
20 Hadassah Hebrew University Medical Center [Jerusalem]
21 OVGU - Otto-von-Guericke-Universität Magdeburg = Otto-von-Guericke University [Magdeburg]
22 Rigshospitalet [Copenhagen]
23 Vanderbilt University [Nashville]
24 Children’s Healthcare of Atlanta
25 CHOP - Children’s Hospital of Philadelphia
26 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence
27 WUSTL - Washington University in Saint Louis
28 UMG - University Medical Center Göttingen
29 Klinikum Augsburg
30 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
31 Radboud University Medical Center [Nijmegen]
32 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
33 DKFZ - German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg]
34 Tübingen University Hospital [Germany]
35 University Hospital Basel [Basel]
36 Hirslanden Medical Center
37 University Hospital Berne
38 Medical Center Bielefeld
39 MUNI - Masaryk University [Brno]
40 Department of Pathology
41 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
42 Hôpital d'Instruction des Armées Sainte Anne
43 IGR - Institut Gustave Roussy
44 Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy]
45 Hôpital Necker - Enfants Malades [AP-HP]
46 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
47 University hospital of Zurich [Zurich]
48 VCU - Virginia Commonwealth University
49 Biocenter University of Würzburg = Biozentrum der Universität Würzburg
50 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
51 NYU Langone Medical Center - New York University Langone Medical Center
52 VU University Medical Center [Amsterdam]
53 Henry Ford Hospital
54 The University of Texas M.D. Anderson Cancer Center [Houston]
55 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
56 McGill University = Université McGill [Montréal, Canada]

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.

Mots clés: CNS-PNETs; DNA Methylation; tumor

Domaines: Cancer; Neurobiologie

Dominik Sturm, Brent A.Orr, Umut H.Toprak, Volker Hovestadt, David T. W. Jones, et al.. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs. Cell, 2016, 164, pp.1060-1072. ⟨10.1016/j.cell.2016.01.015⟩. ⟨hal-01480124⟩