Journal Article

TMOD-29. DEVELOPMENT OF PRECLINICAL GLIOMA MOUSE MODELS FOR GENE FUSIONS

Barbara Oldrini, Carolina Marques and Massimo Squatrito

in Neuro-Oncology

Volume 19, issue suppl_6, pages vi260-vi260
Published in print November 2017 | ISSN: 1522-8517
Published online November 2017 | e-ISSN: 1523-5866 | DOI: https://dx.doi.org/10.1093/neuonc/nox168.1066
TMOD-29. DEVELOPMENT OF PRECLINICAL GLIOMA MOUSE MODELS FOR GENE FUSIONS

Show Summary Details

Preview

Abstract

The occurrence and importance of gene fusions in glioma has been appreciated only recently, largely due to high throughput technologies, and gene fusions have been indicated as one of the major genomic abnormalities in GBM. The functional role of the vast majority of these alterations is completely unexplored. Although these events are rare, not exceeding 1% to 2% per rearrangement. Some of them will be instantly translatable given the accessibility of existing tyrosine kinase inhibitors (TKI) that either have been FDA- approved or are under investigation in other indications. The Trk receptor family comprises three transmembrane proteins indicated as TrkA, TrkB and TrkC receptors, and are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue, and play a critical function in the nervous system through activation by neurotrophins. Recurrent gene fusions involving NTRK1, 2 and 3 genes have been recently identified in both low and high-grade gliomas. Through the use of CRISPR/Cas9 technology we are developing preclinical mouse models of the gene fusions involving the family of the Trk receptor family. We have identified eighteen different fusions involving NTRK genes in gliomas. Our preliminary data on one of those fusions, Bcan-Ntrk1, indicate that we are able to generate gene rearrangements in neuronal stem cells and that this fusion is able to generate tumors in combination with p53 loss in vivo. Cells isolated from these tumors are sensitive to the pan-Trk inhibitor Entrectinib. This approach will be particularly useful to conduct preclinical trials using Trk inhibitors and study possible mechanism of resistance to such inhibitors.

Journal Article.  0 words. 

Subjects: Medical Oncology ; Neurology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content. subscribe or login to access all content.