Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/140338
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Type: | Journal article |
Title: | Recurrent SPECC1L–NTRK fusions in pediatric sarcoma and brain tumors |
Author: | Khuong-Quang, D.-A. Brown, L.M. Wong, M. Mayoh, C. Sexton-Oates, A. Kumar, A. Pinese, M. Nagabushan, S. Lau, L. Ludlow, L.E. Gifford, A.J. Rodriguez, M. Desai, J. Fox, S.B. Haber, M. Ziegler, D.S. Hansford, J.R. Marshall, G.M. Cowley, M.J. Ekert, P.G. |
Citation: | Cold Spring Harbor molecular case studies, 2020; 6(6):a005710-1-a005710-17 |
Publisher: | Cold Spring Harbor Laboratory |
Issue Date: | 2020 |
ISSN: | 2373-2873 2373-2873 |
Statement of Responsibility: | Dong-Anh Khuong-Quang, Lauren M. Brown, Marie Wong, Chelsea Mayoh, Alexandra Sexton-Oates, Amit Kumar, Mark Pinese, Sumanth Nagabushan, Loretta Lau, Louise E. Ludlow, Andrew J. Gifford, Michael Rodriguez, Jayesh Desai, Stephen B. Fox, Michelle Haber, David S. Ziegler, Jordan R. Hansford, Glenn M. Marshall, Mark J. Cowley, and Paul G. Ekert |
Abstract: | The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L–NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. These fusions arose either through a simple balanced rearrangement or in the context of a complex chromoplexy event. We cloned the SPECC1L–NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L–NTRK2 expression are sensitive to a TRK inhibitor drug. We report here that SPECC1L–NTRK fusions can arise in a range of pediatric cancers. Although WGS and RNA-seq are not required to detect NTRK fusions, these techniques may be of benefit when NTRK fusions are not suspected on clinical grounds or not identified by other methods. |
Keywords: | Biomarkers, Tumor Brain Neoplasms Central Nervous System Neoplasms Child Gene Expression Regulation, Neoplastic Humans Infant Membrane Glycoproteins Oncogene Proteins, Fusion Phosphoproteins Protein Kinase Inhibitors Receptor, trkA Receptor, trkB Sarcoma Whole Genome Sequencing |
Rights: | © 2020 Khuong-Quang et al. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
DOI: | 10.1101/mcs.a005710 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1079329 http://purl.org/au-research/grants/nhmrc/1140626 |
Published version: | http://dx.doi.org/10.1101/mcs.a005710 |
Appears in Collections: | Molecular and Biomedical Science publications |
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hdl_140338.pdf | Published version | 7.45 MB | Adobe PDF | View/Open |
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