%0 Journal Article %1 Jones2013 %A Jones, David T W. %A Hutter, Barbara %A Jäger, Natalie %A Korshunov, Andrey %A Kool, Marcel %A Warnatz, Hans-Jörg %A Zichner, Thomas %A Lambert, Sally R. %A Ryzhova, Marina %A Quang, Dong Anh Khuong %A Fontebasso, Adam M. %A Stütz, Adrian M. %A Hutter, Sonja %A Zuckermann, Marc %A Sturm, Dominik %A Gronych, Jan %A Lasitschka, Bärbel %A Schmidt, Sabine %A Seker-Cin, Huriye %A Witt, Hendrik %A Sultan, Marc %A Ralser, Meryem %A Northcott, Paul A. %A Hovestadt, Volker %A Bender, Sebastian %A Pfaff, Elke %A Stark, Sebastian %A Faury, Damien %A Schwartzentruber, Jeremy %A Majewski, Jacek %A Weber, Ursula D. %A Zapatka, Marc %A Raeder, Benjamin %A Schlesner, Matthias %A Worth, Catherine L. %A Bartholomae, Cynthia C. %A von Kalle, Christof %A Imbusch, Charles D. %A Radomski, Sylwester %A Lawerenz, Chris %A van Sluis, Peter %A Koster, Jan %A Volckmann, Richard %A Versteeg, Rogier %A Lehrach, Hans %A Monoranu, Camelia %A Winkler, Beate %A Unterberg, Andreas %A Herold-Mende, Christel %A Milde, Till %A Kulozik, Andreas E. %A Ebinger, Martin %A Schuhmann, Martin U. %A Cho, Yoon-Jae %A Pomeroy, Scott L. %A von Deimling, Andreas %A Witt, Olaf %A Taylor, Michael D. %A Wolf, Stephan %A Karajannis, Matthias A. %A Eberhart, Charles G. %A Scheurlen, Wolfram %A Hasselblatt, Martin %A Ligon, Keith L. %A Kieran, Mark W. %A Korbel, Jan O. %A Yaspo, Marie-Laure %A Brors, Benedikt %A Felsberg, Jörg %A Reifenberger, Guido %A Collins, V Peter %A Jabado, Nada %A Eils, Roland %A Lichter, Peter %A Pfister, Stefan M. %A International Cancer Genome Consortium PedBrain Tumor Project, %D 2013 %J Nat Genet %K 1, 6; 9; Animals; Astrocytoma, B-raf, Base Brain Breakpoints; Cell Chromosome Chromosomes, Conformation; Factor, Factors, Fibroblast Fusion, Growth Human, Humans; Kinase Line; MAP Mice; Models, Molecular; Mutation; Neoplasms, Neoplastic, Oncogene Pair Protein Proteins Proteins, Proto-Oncogene Receptor, Sequence; Signaling System; Transformation, Type chemistry/genetics; genetics/metabolism genetics/metabolism; metabolism; trkB, %N 8 %P 927--932 %R 10.1038/ng.2682 %T Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. %U http://dx.doi.org/10.1038/ng.2682 %V 45 %X 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.

@article{Jones2013, __markedentry = {[bbrors:6]}, 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.}, added-at = {2015-04-09T12:36:21.000+0200}, author = {Jones, David T W. and Hutter, Barbara and J{\"{a}}ger, Natalie and Korshunov, Andrey and Kool, Marcel and Warnatz, Hans-J{\"{o}}rg and Zichner, Thomas and Lambert, Sally R. and Ryzhova, Marina and Quang, Dong Anh Khuong and Fontebasso, Adam M. and St{\"{u}}tz, Adrian M. and Hutter, Sonja and Zuckermann, Marc and Sturm, Dominik and Gronych, Jan and Lasitschka, B{\"{a}}rbel and Schmidt, Sabine and Seker-Cin, Huriye and Witt, Hendrik and Sultan, Marc and Ralser, Meryem and Northcott, Paul A. and Hovestadt, Volker and Bender, Sebastian and Pfaff, Elke and Stark, Sebastian and Faury, Damien and Schwartzentruber, Jeremy and Majewski, Jacek and Weber, Ursula D. and Zapatka, Marc and Raeder, Benjamin and Schlesner, Matthias and Worth, Catherine L. and Bartholomae, Cynthia C. and {von Kalle}, Christof and Imbusch, Charles D. and Radomski, Sylwester and Lawerenz, Chris and {van Sluis}, Peter and Koster, Jan and Volckmann, Richard and Versteeg, Rogier and Lehrach, Hans and Monoranu, Camelia and Winkler, Beate and Unterberg, Andreas and Herold-Mende, Christel and Milde, Till and Kulozik, Andreas E. and Ebinger, Martin and Schuhmann, Martin U. and Cho, Yoon-Jae and Pomeroy, Scott L. and {von Deimling}, Andreas and Witt, Olaf and Taylor, Michael D. and Wolf, Stephan and Karajannis, Matthias A. and Eberhart, Charles G. and Scheurlen, Wolfram and Hasselblatt, Martin and Ligon, Keith L. and Kieran, Mark W. and Korbel, Jan O. and Yaspo, Marie-Laure and Brors, Benedikt and Felsberg, J{\"{o}}rg and Reifenberger, Guido and Collins, V Peter and Jabado, Nada and Eils, Roland and Lichter, Peter and Pfister, Stefan M. and {International Cancer Genome Consortium PedBrain Tumor Project}}, biburl = {https://www.bibsonomy.org/bibtex/2d0fed8552e458d5aa273ba5099299878/bbrors}, doi = {10.1038/ng.2682}, institution = {logy, German Cancer Research Center (DKFZ), Heidelberg, Germany.}, interhash = {0a11b8ec11f15387682ebb0e82505c29}, intrahash = {d0fed8552e458d5aa273ba5099299878}, journal = {Nat Genet}, keywords = {1, 6; 9; Animals; Astrocytoma, B-raf, Base Brain Breakpoints; Cell Chromosome Chromosomes, Conformation; Factor, Factors, Fibroblast Fusion, Growth Human, Humans; Kinase Line; MAP Mice; Models, Molecular; Mutation; Neoplasms, Neoplastic, Oncogene Pair Protein Proteins Proteins, Proto-Oncogene Receptor, Sequence; Signaling System; Transformation, Type chemistry/genetics; genetics/metabolism genetics/metabolism; metabolism; trkB,}, language = {eng}, medline-pst = {ppublish}, month = Aug, number = 8, owner = {bbrors}, pages = {927--932}, pii = {ng.2682}, pmid = {23817572}, timestamp = {2015-04-09T12:36:21.000+0200}, title = {Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma.}, url = {http://dx.doi.org/10.1038/ng.2682}, volume = 45, year = 2013 }