NTRK1 fusion in glioblastoma multiforme.
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with 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 fus...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3960150?pdf=render |
| _version_ | 1818942723268280320 |
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| author | Jinkuk Kim Yeri Lee Hee Jin Cho Young-Eun Lee Jaeyeol An Gye-Hyun Cho Young-Hyeh Ko Kyeung Min Joo Do-Hyun Nam |
| author_facet | Jinkuk Kim Yeri Lee Hee Jin Cho Young-Eun Lee Jaeyeol An Gye-Hyun Cho Young-Hyeh Ko Kyeung Min Joo Do-Hyun Nam |
| author_sort | Jinkuk Kim |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with 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 fusion genes in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA), and found that 3' exons of neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA) are fused to 5' exons of the genes that are highly expressed in neuronal tissues, neurofascin (NFASC) and brevican (BCAN). The fusions preserved both the transmembrane and kinase domains of NTRK1 in frame. 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 lacked NTRK1 expression, the fusion-positive GBMs expressed fusion transcripts in high abundance, and showed elevated NTRK1-pathway activity. Lentiviral transduction of the NFASC-NTRK1 fusion gene in NIH 3T3 cells increased proliferation in vitro, colony formation in soft agar, and tumor formation in mice, suggesting the possibility that the fusion contributed to the initiation or maintenance of the fusion-positive GBMs, and therefore may be a rational drug target. |
| first_indexed | 2024-12-20T07:15:58Z |
| format | Article |
| id | doaj.art-75df8a3b8b45418cb8e73fe826e54187 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T07:15:58Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-75df8a3b8b45418cb8e73fe826e541872022-12-21T19:48:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9194010.1371/journal.pone.0091940NTRK1 fusion in glioblastoma multiforme.Jinkuk KimYeri LeeHee Jin ChoYoung-Eun LeeJaeyeol AnGye-Hyun ChoYoung-Hyeh KoKyeung Min JooDo-Hyun NamGlioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with 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 fusion genes in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA), and found that 3' exons of neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA) are fused to 5' exons of the genes that are highly expressed in neuronal tissues, neurofascin (NFASC) and brevican (BCAN). The fusions preserved both the transmembrane and kinase domains of NTRK1 in frame. 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 lacked NTRK1 expression, the fusion-positive GBMs expressed fusion transcripts in high abundance, and showed elevated NTRK1-pathway activity. Lentiviral transduction of the NFASC-NTRK1 fusion gene in NIH 3T3 cells increased proliferation in vitro, colony formation in soft agar, and tumor formation in mice, suggesting the possibility that the fusion contributed to the initiation or maintenance of the fusion-positive GBMs, and therefore may be a rational drug target.http://europepmc.org/articles/PMC3960150?pdf=render |
| spellingShingle | Jinkuk Kim Yeri Lee Hee Jin Cho Young-Eun Lee Jaeyeol An Gye-Hyun Cho Young-Hyeh Ko Kyeung Min Joo Do-Hyun Nam NTRK1 fusion in glioblastoma multiforme. PLoS ONE |
| title | NTRK1 fusion in glioblastoma multiforme. |
| title_full | NTRK1 fusion in glioblastoma multiforme. |
| title_fullStr | NTRK1 fusion in glioblastoma multiforme. |
| title_full_unstemmed | NTRK1 fusion in glioblastoma multiforme. |
| title_short | NTRK1 fusion in glioblastoma multiforme. |
| title_sort | ntrk1 fusion in glioblastoma multiforme |
| url | http://europepmc.org/articles/PMC3960150?pdf=render |
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