Recurrent MET fusion genes represent a drug target in pediatric glioblastoma

for the International Cancer Genome Consortium PedBrain Tumor Project

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

171 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1314-1320
Aantal pagina's7
TijdschriftNature Medicine
Volume22
Nummer van het tijdschrift11
DOI's
StatusGepubliceerd - 1 nov. 2016
Extern gepubliceerdJa

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