Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-08

AUTHORS

David T W Jones, Barbara Hutter, Natalie Jäger, Andrey Korshunov, Marcel Kool, Hans-Jörg Warnatz, Thomas Zichner, Sally R Lambert, Marina Ryzhova, Dong Anh Khuong Quang, Adam M Fontebasso, Adrian M Stütz, Sonja Hutter, Marc Zuckermann, Dominik Sturm, Jan Gronych, Bärbel Lasitschka, Sabine Schmidt, Huriye Şeker-Cin, Hendrik Witt, Marc Sultan, Meryem Ralser, Paul A Northcott, Volker Hovestadt, Sebastian Bender, Elke Pfaff, Sebastian Stark, Damien Faury, Jeremy Schwartzentruber, Jacek Majewski, Ursula D Weber, Marc Zapatka, Benjamin Raeder, Matthias Schlesner, Catherine L Worth, Cynthia C Bartholomae, Christof von Kalle, Charles D Imbusch, Sylwester Radomski, Chris Lawerenz, Peter van Sluis, Jan Koster, Richard Volckmann, Rogier Versteeg, Hans Lehrach, Camelia Monoranu, Beate Winkler, Andreas Unterberg, Christel Herold-Mende, Till Milde, Andreas E Kulozik, Martin Ebinger, Martin U Schuhmann, Yoon-Jae Cho, Scott L Pomeroy, Andreas von Deimling, Olaf Witt, Michael D Taylor, Stephan Wolf, Matthias A Karajannis, Charles G Eberhart, Wolfram Scheurlen, Martin Hasselblatt, Keith L Ligon, Mark W Kieran, Jan O Korbel, Marie-Laure Yaspo, Benedikt Brors, Jörg Felsberg, Guido Reifenberger, V Peter Collins, Nada Jabado, Roland Eils, Peter Lichter, International Cancer Genome Consortium PedBrain Tumor Project, Stefan M Pfister

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. More... »

PAGES

927

References to SciGraph publications

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    8

    VOLUME

    45

    Related Patents

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2682

    DOI

    http://dx.doi.org/10.1038/ng.2682

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1009937083

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23817572


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