Recurrent MET fusion genes represent a drug target in pediatric glioblastoma.
Loading...
ICR Authors
Authors
International Cancer Genome Consortium PedBrain Tumor Project,
Document Type
Journal Article
Date
2016-11-01
Date Accepted
2016-09-15
Date Available
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.
Citation
Nature medicine, 2016, 22 (11), pp. 1314 - 1320
DOI
Rights
Source Title
Publisher
NATURE PORTFOLIO
ISSN
1078-8956
eISSN
1546-170X
Collections
Research Team
Glioma Team