Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma

被引：607

作者：

Jones, David T. W. ^{[1
]}

Hutter, Barbara ^{[2
]}

Jaeger, Natalie ^{[2
]}

Korshunov, Andrey ^{[3
,4
]}

Kool, Marcel ^{[1
]}

Warnatz, Hans-Joerg ^{[5
]}

Zichner, Thomas ^{[6
]}

Lambert, Sally R. ^{[7
]}

Ryzhova, Marina ^{[8
]}

Dong Anh Khuong Quang ^{[9
]}

Fontebasso, Adam M. ^{[9
]}

Stuetz, Adrian M. ^{[6
]}

Hutter, Sonja ^{[1
]}

Zuckermann, Marc ^{[10
]}

Sturm, Dominik ^{[1
]}

Gronych, Jan ^{[10
]}

Lasitschka, Baerbel ^{[11
]}

Schmidt, Sabine ^{[11
]}

Seker-Cin, Huriye ^{[1
]}

Witt, Hendrik ^{[1
,12
]}

Sultan, Marc ^{[5
]}

Ralser, Meryem ^{[5
]}

Northcott, Paul A. ^{[1
]}

Hovestadt, Volker ^{[10
]}

Bender, Sebastian ^{[1
]}

Pfaff, Elke ^{[1
]}

Stark, Sebastian ^{[1
]}

Faury, Damien ^{[9
]}

Schwartzentruber, Jeremy ^{[13
,14
]}

Majewski, Jacek ^{[13
,14
]}

Weber, Ursula D. ^{[10
]}

Zapatka, Marc ^{[10
]}

Raeder, Benjamin ^{[6
]}

Schlesner, Matthias ^{[2
]}

Worth, Catherine L. ^{[5
]}

Bartholomae, Cynthia C. ^{[15
,16
]}

von Kalle, Christof ^{[15
,16
,17
]}

Imbusch, Charles D. ^{[2
]}

Radomski, Sylwester ^{[2
,18
,19
]}

Lawerenz, Chris ^{[2
]}

van Sluis, Peter ^{[20
]}

Koster, Jan ^{[20
]}

Volckmann, Richard ^{[20
]}

Versteeg, Rogier ^{[20
]}

Lehrach, Hans ^{[5
]}

Monoranu, Camelia ^{[21
]}

Winkler, Beate ^{[22
]}

Unterberg, Andreas ^{[23
]}

Herold-Mende, Christel ^{[23
]}

Milde, Till ^{[12
,24
]}

机构：

[1] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[2] DKFZ, Div Theoret Bioinformat, Heidelberg, Germany

[3] Heidelberg Univ, Dept Neuropathol, Heidelberg, Germany

[4] DKFZ, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[5] Max Planck Inst Mol Genet, D-14195 Berlin, Germany

[6] European Mol Biol Lab, Genome Biol Unit, D-69012 Heidelberg, Germany

[7] Univ Cambridge, Dept Pathol, Div Mol Histopathol, Cambridge CB2 1QP, England

[8] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow, Russia

[9] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[10] DKFZ, Div Mol Genet, Heidelberg, Germany

[11] DKFZ, Genom & Prote Core Facil, Heidelberg, Germany

[12] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[13] McGill Univ, Montreal, PQ, Canada

[14] Genome Quebec Innovat Ctr, Montreal, PQ, Canada

[15] DKFZ, Div Translat Oncol, Heidelberg, Germany

[16] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[17] Heidelberg Ctr Personalised Oncol DKFZ HIPO, Heidelberg, Germany

[18] Heidelberg Univ, IPMB, Heidelberg, Germany

[19] Heidelberg Univ, BioQuant Ctr, Heidelberg, Germany

[20] Univ Amsterdam, Amsterdam Med Ctr, Dept Oncogen, Amsterdam, Netherlands

[21] Univ Wurzburg, Inst Pathol, Dept Neuropathol, Wurzburg, Germany

[22] Childrens Univ Hosp Wurzburg, Dept Pediat Hematol & Oncol, Wurzburg, Germany

[23] Univ Heidelberg Hosp, Dept Neurosurg, Heidelberg, Germany

[24] DKFZ, Clin Cooperat Unit Pediat Oncol, Heidelberg, Germany

[25] Childrens Univ Hosp, Dept Hematol & Oncol, Tubingen, Germany

[26] Univ Hosp, Dept Neurosurg, Tubingen, Germany

[27] Stanford Univ, Div Child Neurol, Palo Alto, CA 94304 USA

[28] Boston Childrens Hosp, Dept Neurol, Boston, MA USA

[29] Broad Inst MIT & Harvard, Cambridge, MA USA

[30] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada

[31] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada

[32] NYU, Langone Med Ctr, Hassenfeld Childrens Ctr Canc & Blood Disorders, New York, NY USA

[33] Johns Hopkins Univ, Sch Med, Div Pathol, Baltimore, MD USA

[34] Nurnberg Childrens Hosp, Cnopfsche Kinderklin, Nurnberg, Germany

[35] Univ Hosp Munster, Inst Neuropathol, Munster, Germany

[36] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA

[37] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[38] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[39] Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany

[40] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Paediat, Montreal, PQ H3H 1P3, Canada

来源：

NATURE GENETICS | 2013年 / 45卷 / 08期

基金：

美国国家卫生研究院;

关键词：

MAPK PATHWAY ACTIVATION; MUTATIONAL PROCESSES; SIGNAL-TRANSDUCTION; DISTINCT SUBGROUPS; NOONAN-SYNDROME; HISTONE H3.3; PAIRED-END; CANCER; GROWTH; GENES;

D O I：

10.1038/ng.2682

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pilocytic astrocytoma, the most common childhood brain tumor(1), is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations(2). Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression(3) and often becoming a chronic disease with substantial morbidities(4). 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(5). Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.

引用

页码：927 / U295

页数：8

共 77 条

[1] Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling [J].

Agazie, YM ;

Hayman, MJ .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (21) :7875-7886

[2]

[Anonymous], STAT REP PRIM BRAIN

[3] Survival and long-term health and cognitive outcomes after low-grade glioma [J].

Armstrong, Gregory T. ;

Conklin, Heather M. ;

Huang, Sujuan ;

Srivastava, Deokumar ;

Sanford, Robert ;

Ellison, David W. ;

Merchant, Thomas E. ;

Hudson, Melissa M. ;

Hoehn, Mary Ellen ;

Robison, Leslie L. ;

Gajjar, Amar ;

Morris, E. Brannon .

NEURO-ONCOLOGY, 2011, 13 (02) :223-234

[4] Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor [J].

Breitenbuecher, Frank ;

Schnittger, Susanne ;

Grundler, Rebekka ;

Markova, Boyka ;

Carius, Birgit ;

Brecht, Alexandra ;

Duyster, Justus ;

Haferlach, Torsten ;

Huber, Christoph ;

Fischer, Thomas .

BLOOD, 2009, 113 (17) :4074-4077

[5] The tyrosine phosphatase Shp2 (PTPN11) in cancer [J].

Chan, Gordon ;

Kalaitzidis, Demetrios ;

Neel, Benjamin G. .

CANCER AND METASTASIS REVIEWS, 2008, 27 (02) :179-192

[6] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[7] Oncogenic FAM131B-BRAF fusion resulting from 7q34 deletion comprises an alternative mechanism of MAPK pathway activation in pilocytic astrocytoma [J].

Cin, Huriye ;

Meyer, Claus ;

Herr, Ricarda ;

Janzarik, Wibke G. ;

Lambert, Sally ;

Jones, David T. W. ;

Jacob, Karine ;

Benner, Axel ;

Witt, Hendrik ;

Remke, Marc ;

Bender, Sebastian ;

Falkenstein, Fabian ;

Ton Nu Van Anh ;

Olbrich, Heike ;

von Deimling, Andreas ;

Pekrun, Arnulf ;

Kulozik, Andreas E. ;

Gnekow, Astrid ;

Scheurlen, Wolfram ;

Witt, Olaf ;

Omran, Heymut ;

Jabado, Nada ;

Collins, V. Peter ;

Brummer, Tilman ;

Marschalek, Rolf ;

Lichter, Peter ;

Korshunov, Andrey ;

Pfister, Stefan M. .

ACTA NEUROPATHOLOGICA, 2011, 121 (06) :763-774

[8] MuSiC: Identifying mutational significance in cancer genomes [J].

Dees, Nathan D. ;

Zhang, Qunyuan ;

Kandoth, Cyriac ;

Wendl, Michael C. ;

Schierding, William ;

Koboldt, Daniel C. ;

Mooney, Thomas B. ;

Callaway, Matthew B. ;

Dooling, David ;

Mardis, Elaine R. ;

Wilson, Richard K. ;

Ding, Li .

GENOME RESEARCH, 2012, 22 (08) :1589-1598

[9]

Dewitt J, 2013, ONCOGENE, DOI [10.1038/onc.2013.39, DOI 10.1038/0NC.2013.39]

[10] Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives [J].

Dieci, Maria Vittoria ;

Arnedos, Monica ;

Andre, Fabrice ;

Soria, Jean Charles .

CANCER DISCOVERY, 2013, 3 (03) :264-279

← 1 2 3 4 5 6 7 8 →