Abstract 1765: Recurrent fusion of NTRK1 in glioblastoma multiforme

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 1765
• Main Authors: Kim, Jinkuk, Cho, Hee-Jin, Cho, Gye-Hyun, Ko, Young-Hyeh, Paik, Soonmyung, Nam, Do-Hyun
• Format: Journal Article
• Language: English
• Published: 15.04.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-1765

Abstract Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with substantial survival benefit. Recent studies on many types of solid tumors showed that fusion genes often play driver roles and are promising targets for pharmaceutical intervention. To survey potential fusion genes in GBM, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA). From the analysis, we identified recurrent fusion of neurotrophic tyrosine kinase receptor type 1 (NTRK1, also called TrkA) to the genes highly expressed in neuronal tissues, neurofascin (NFASC) and brevican (BCAN). NTRK1 is a mediator of the pro-survival signaling of nerve growth factor (NGF) and is a known oncogene, found commonly altered in human cancer. While GBMs largely lack NTRK1 expression, the fusion-positive GBMs express fusion transcripts in high abundance that retain NTRK1 kinase domain in frame. Analyses of the matching Exome-Seq data indicated that NFASC-NTRK1 fusion occurred through DNA-level rearrangement, whereas BCAN-NTRK1 fusion presumably occurred at RNA-level. As analogous NTRK1-fusions with thyroid-expressed genes were previously shown to drive thyroid cancer, NTRK1-fusion in GBM might have a similar role. Consistent with this hypothesis, the GBMs that harbor the NTRK1-fusion showed elevated NGF/NTRK1 pathway activity. About 1% of GBM patients are estimated to have NTRK1-fusion; these patients might benefit from potential NTRK1 inhibition therapies. Citation Format: Jinkuk Kim, Hee-Jin Cho, Gye-Hyun Cho, Young-Hyeh Ko, Soonmyung Paik, Do-Hyun Nam. Recurrent fusion of NTRK1 in glioblastoma multiforme. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1765. doi:10.1158/1538-7445.AM2013-1765 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.