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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., Hutter, B., Jäger, N., Korshunov, A., Kool, M., Warnatz, H.J., Zichner, T., Lambert, S.R., Ryzhova, M., Quang, D.A.K., Fontebasso, A.M., Stütz, A.M., Hutter, S., Zuckermann, M., Sturm, D., Gronych, J., Lasitschka, B., Schmidt, S., Seker-Cin, H., Witt, H., Sultan, M., Ralser, M., Northcott, P.A., Hovestadt, V., Bender, S., Pfaff, E., Stark, S., Faury, D., Schwartzentruber, J., Majewski, J., Weber, U.D., Zapatka, M., Raeder, B., Schlesner, M., Worth, C.L., Bartholomae, C.C., von Kalle, C., Imbusch, C.D., Radomski, S., Lawerenz, C., van Sluis, P., Koster, J., Volckmann, R., Versteeg, R., Lehrach, H., Monoranu, C., Winkler, B., Unterberg, A., Herold-Mende, C., Milde, T., Kulozik, A.E., Ebinger, M., Schuhmann, M.U., Cho, Y.J., Pomeroy, S.L., von Deimling, A., Witt, O., Taylor, M.D., Wolf, S., Karajannis, M.A., Eberhart, C.G., Scheurlen, W., Hasselblatt, M., Ligon, K.L., Kieran, M.W., Korbel, J.O., Yaspo, M.L., Brors, B., Felsberg, J., Reifenberger, G., Collins, V.P., Jabado, N., Eils, R., 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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