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

• Authors: 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.; BUEREN André O. von; HOFF Katja von; RUTKOWSKI Stefan; HEROLD-MENDE Christel; FRÜHWALD Michael C.; MILDE Till; HASSELBLATT Martin; WESSELING Pieter; RÖ?LER 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; METER Timothy van; MONORANU Camelia-Maria; FELSBERG Jörg; REIFENBERGER Guido; SNUDERL Matija; FORRESTER Lynn Ann; KOSTER Jan; VERSTEEG Rogier; VOLCKMANN Richard; SLUIS Peter van; WOLF Stephan; MIKKELSEN Tom; GAJJAR Amar; ALDAPE Kenneth; MOORE Andrew S.; TAYLOR Michael D.; JONES Chris; JABADO Nada; KARAJANNIS Matthias A.; EILS Ronald; SCHLESNER Matthias; LICHTER Peter; DEIMLING Andreas von; PFISTER Stefan M.; ELLISON David W.; KORSHUNOV Andrey; KOOL Marcel
• Year of publication: 2016
• Type: Article in Periodical
• Magazine / Source: Cell
• MU Faculty or unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1016/j.cell.2016.01.015
• Field: Oncology and hematology
• Keywords: PRIMITIVE NEUROECTODERMAL TUMORS; CENTRAL-NERVOUS-SYSTEM; GENOMIC ANALYSIS; ABUNDANT NEUROPIL; TRUE ROSETTES; MUTATIONS; DNA; MEDULLOBLASTOMA; METHYLATION; AMPLIFICATION
• Description: 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.