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@ARTICLE{Bender:125497,
author = {S. Bender$^*$ and J. Gronych and H.-J. Warnatz and B.
Hutter$^*$ and S. Gröbner and M. Ryzhova and E. Pfaff$^*$
and V. Hovestadt and F. Weinberg and S. Halbach and M.
Kool$^*$ and P. A. Northcott and D. Sturm and L. Bjerke and
T. Zichner and A. M. Stütz and K. Schramm and B. Huang and
I. Buchhalter$^*$ and M. Heinold$^*$ and T. Risch and B. C.
Worst and C. M. van Tilburg and U. D. Weber and M.
Zapatka$^*$ and B. Raeder and D. Milford and S. Heiland and
C. von Kalle$^*$ and C. Previti and C. Lawerenz$^*$ and A.
E. Kulozik and A. Unterberg and O. Witt$^*$ and A. von
Deimling$^*$ and D. Capper$^*$ and N. Truffaux and J. Grill
and N. Jabado and A. M. Sehested and D. Sumerauer and D. H.
Brahim and S. Trabelsi and H.-K. Ng and D. Zagzag and J. C.
Allen and M. A. Karajannis and N. G. Gottardo and C. Jones
and J. O. Korbel and S. Schmidt$^*$ and S. Wolf$^*$ and G.
Reifenberger and J. Felsberg and B. Brors$^*$ and C.
Herold-Mende and H. Lehrach and T. Brummer and A. Korshunov
and R. Eils$^*$ and M.-L. Yaspo and S. Pfister$^*$ and P.
Lichter$^*$ and D. Jones$^*$},
collaboration = {, , International Cancer Genome Consortium PedBrain Tumor
Project.},
title = {{R}ecurrent {MET} fusion genes represent a drug target in
pediatric glioblastoma.},
journal = {Nature medicine},
volume = {22},
number = {11},
issn = {1546-170X},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DKFZ-2017-01623},
pages = {1314 - 1320},
year = {2016},
note = {Bender S*, Gronych J*, Warnatz HJ*, Hutter B*(*shared first
and senior authorships)Pfister SM*, Lichter P*, Jones DT*},
abstract = {Pediatric glioblastoma is one of the most common and most
deadly brain tumors in childhood. Using an integrative
genetic analysis of 53 pediatric glioblastomas and five in
vitro model systems, we identified previously unidentified
gene fusions involving the MET oncogene in $∼10\%$ of
cases. These MET fusions activated mitogen-activated protein
kinase (MAPK) signaling and, in cooperation with lesions
compromising cell cycle regulation, induced aggressive glial
tumors in vivo. MET inhibitors suppressed MET tumor growth
in xenograft models. Finally, we treated a pediatric patient
bearing a MET-fusion-expressing glioblastoma with the
targeted inhibitor crizotinib. This therapy led to
substantial tumor shrinkage and associated relief of
symptoms, but new treatment-resistant lesions appeared,
indicating that combination therapies are likely necessary
to achieve a durable clinical response.},
keywords = {Anilides (NLM Chemicals) / DNA, Neoplasm (NLM Chemicals) /
GSK 1363089 (NLM Chemicals) / Microtubule-Associated
Proteins (NLM Chemicals) / Oncogene Proteins, Fusion (NLM
Chemicals) / Protein Kinase Inhibitors (NLM Chemicals) /
Proteins (NLM Chemicals) / Pyrazoles (NLM Chemicals) /
Pyridines (NLM Chemicals) / Quinolines (NLM Chemicals) /
RNA, Messenger (NLM Chemicals) / TFG protein, human (NLM
Chemicals) / cytoplasmic linker protein 115 (NLM Chemicals)
/ crizotinib (NLM Chemicals) / Proto-Oncogene Proteins c-met
(NLM Chemicals) / Mitogen-Activated Protein Kinases (NLM
Chemicals) / PTPRZ1 protein, human (NLM Chemicals) /
Receptor-Like Protein Tyrosine Phosphatases, Class 5 (NLM
Chemicals)},
cin = {G100 / G200 / B062 / B060 / G010 / G340 / G380 / W190 /
B080 / L101 / L601 / L401},
ddc = {610},
cid = {I:(DE-He78)G100-20160331 / I:(DE-He78)G200-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)B060-20160331 /
I:(DE-He78)G010-20160331 / I:(DE-He78)G340-20160331 /
I:(DE-He78)G380-20160331 / I:(DE-He78)W190-20160331 /
I:(DE-He78)B080-20160331 / I:(DE-He78)L101-20160331 /
I:(DE-He78)L601-20160331 / I:(DE-He78)L401-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27748748},
doi = {10.1038/nm.4204},
url = {https://inrepo02.dkfz.de/record/125497},
}