NTRK1 Fusion in Glioblastoma Multiforme

• DOI: 10.1371/journal.pone.0091940
• Publication Date: 2014-03-20T02:50:52Z
• Authors: Jinkuk Kim; Yeri Lee; Hee-Jin Cho; Young-Eun Lee; Jaeyeol An; Gye-Hyun Cho; Young-Hyeh Ko; Kyeung Min Joo; Do-Hyun Nam
• Keywords: Male; Oncogene Proteins, Fusion; Carcinogenesis; Science; Molecular Sequence Data; Mice, Nude; Mice; 03 medical and health sciences; Animals; Amino Acid Sequence; Nerve Growth Factors; Receptor, trkA; Mice, Inbred BALB C; 0303 health sciences; Base Sequence; Brain Neoplasms; Q; R; 3. Good health; NIH 3T3 Cells; Medicine; Glioblastoma; Cell Adhesion Molecules; Research Article; Brevican

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy substantial survival benefit. Recent studies on solid tumors showed that fusion genes often play driver roles and are promising targets for pharmaceutical intervention. To survey potential in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA), found 3′ exons neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA) fused to 5′ highly expressed neuronal tissues, neurofascin (NFASC) brevican (BCAN). fusions preserved both transmembrane domains NTRK1 frame. a mediator pro-survival signaling nerve growth factor (NGF) known oncogene, commonly altered human cancer. While GBMs largely lacked expression, fusion-positive transcripts high abundance, elevated NTRK1-pathway activity. Lentiviral transduction NFASC-NTRK1 gene NIH 3T3 cells increased proliferation vitro, colony formation soft agar, tumor mice, suggesting possibility contributed initiation or maintenance therefore may be rational drug target.