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Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma

Item Type:Article
Title:Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma
Creators Name:Jones, D.T.W. and Hutter, B. and Jäger, N. and Korshunov, A. and Kool, M. and Warnatz, H.J. and Zichner, T. and Lambert, S.R. and Ryzhova, M. and Quang, D.A.K. and Fontebasso, A.M. and Stütz, A.M. and Hutter, S. and Zuckermann, M. and Sturm, D. and Gronych, J. and Lasitschka, B. and Schmidt, S. and Seker-Cin, H. and Witt, H. and Sultan, M. and Ralser, M. and Northcott, P.A. and Hovestadt, V. and Bender, S. and Pfaff, E. and Stark, S. and Faury, D. and Schwartzentruber, J. and Majewski, J. and Weber, U.D. and Zapatka, M. and Raeder, B. and Schlesner, M. and Worth, C.L. and Bartholomae, C.C. and von Kalle, C. and Imbusch, C.D. and Radomski, S. and Lawerenz, C. and van Sluis, P. and Koster, J. and Volckmann, R. and Versteeg, R. and Lehrach, H. and Monoranu, C. and Winkler, B. and Unterberg, A. and Herold-Mende, C. and Milde, T. and Kulozik, A.E. and Ebinger, M. and Schuhmann, M.U. and Cho, Y.J. and Pomeroy, S.L. and von Deimling, A. and Witt, O. and Taylor, M.D. and Wolf, S. and Karajannis, M.A. and Eberhart, C.G. and Scheurlen, W. and Hasselblatt, M. and Ligon, K.L. and Kieran, M.W. and Korbel, J.O. and Yaspo, M.L. and Brors, B. and Felsberg, J. and Reifenberger, G. and Collins, V.P. and Jabado, N. and Eils, R. and Lichter, P. and Pfister, S.M.
Abstract:Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression and often becoming a chronic disease with substantial morbidities. Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF-activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in the NF1 gene. Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.
Keywords:CNS Cancer, DNA Sequencing, Genomics, Oncogenes, Animals, Mice
Source:Nature Genetics
Publisher:Nature Publishing Group
Page Range:927-932
Date:August 2013
Official Publication:https://doi.org/10.1038/ng.2682
PubMed:View item in PubMed

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