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Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas
Gene fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. Using RNA-sequencing, we interrogated a large cohort of gliomas to assess for the incidence of targetable genetic fusions. Gliomas (n = 390) were profiled using the ArcherDx FusionPlex Assay. F...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961205/ https://www.ncbi.nlm.nih.gov/pubmed/29718398 http://dx.doi.org/10.1093/jnen/nly022 |
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author | Ferguson, Sherise D Zhou, Shouhao Huse, Jason T de Groot, John F Xiu, Joanne Subramaniam, Deepa S Mehta, Shwetal Gatalica, Zoran Swensen, Jeffrey Sanai, Nader Spetzler, David Heimberger, Amy B |
author_facet | Ferguson, Sherise D Zhou, Shouhao Huse, Jason T de Groot, John F Xiu, Joanne Subramaniam, Deepa S Mehta, Shwetal Gatalica, Zoran Swensen, Jeffrey Sanai, Nader Spetzler, David Heimberger, Amy B |
author_sort | Ferguson, Sherise D |
collection | PubMed |
description | Gene fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. Using RNA-sequencing, we interrogated a large cohort of gliomas to assess for the incidence of targetable genetic fusions. Gliomas (n = 390) were profiled using the ArcherDx FusionPlex Assay. Fifty-two gene targets were analyzed and fusions with preserved kinase domains were investigated. Overall, 36 gliomas (9%) harbored a total of 37 potentially targetable fusions, the majority of which were found in astrocytomas (n = 34). Within this lineage 11% (25/235) of glioblastomas, 12% (5/42) of anaplastic astrocytomas, 8% (2/25) of grade II astrocytomas, and 33% (2/6) of pilocytic astrocytoma harbored targetable fusions. Fusions were significantly more frequent in IDH wild-type tumors (12%, n = 31/261) relative to IDH mutants (4%; n = 4/109) (p = 0.011). No fusions were seen in oligodendrogliomas. The most frequently observed therapeutically targetable fusions were in FGFR (n = 12), MET (n = 11), and NTRK (n = 8). Several additional novel fusions that have not been previously described in gliomas were identified including EGFR:VWC2 and FGFR3:NBR1. In summary, targetable gene fusions are enriched in IDH wild-type high-grade astrocytic tumors, which will influence enrollment in and interpretation of clinical trials of glioma patients. |
format | Online Article Text |
id | pubmed-5961205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59612052018-06-06 Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas Ferguson, Sherise D Zhou, Shouhao Huse, Jason T de Groot, John F Xiu, Joanne Subramaniam, Deepa S Mehta, Shwetal Gatalica, Zoran Swensen, Jeffrey Sanai, Nader Spetzler, David Heimberger, Amy B J Neuropathol Exp Neurol Original Articles Gene fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. Using RNA-sequencing, we interrogated a large cohort of gliomas to assess for the incidence of targetable genetic fusions. Gliomas (n = 390) were profiled using the ArcherDx FusionPlex Assay. Fifty-two gene targets were analyzed and fusions with preserved kinase domains were investigated. Overall, 36 gliomas (9%) harbored a total of 37 potentially targetable fusions, the majority of which were found in astrocytomas (n = 34). Within this lineage 11% (25/235) of glioblastomas, 12% (5/42) of anaplastic astrocytomas, 8% (2/25) of grade II astrocytomas, and 33% (2/6) of pilocytic astrocytoma harbored targetable fusions. Fusions were significantly more frequent in IDH wild-type tumors (12%, n = 31/261) relative to IDH mutants (4%; n = 4/109) (p = 0.011). No fusions were seen in oligodendrogliomas. The most frequently observed therapeutically targetable fusions were in FGFR (n = 12), MET (n = 11), and NTRK (n = 8). Several additional novel fusions that have not been previously described in gliomas were identified including EGFR:VWC2 and FGFR3:NBR1. In summary, targetable gene fusions are enriched in IDH wild-type high-grade astrocytic tumors, which will influence enrollment in and interpretation of clinical trials of glioma patients. Oxford University Press 2018-06 2018-04-27 /pmc/articles/PMC5961205/ /pubmed/29718398 http://dx.doi.org/10.1093/jnen/nly022 Text en © 2018 American Association of Neuropathologists, Inc. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contactjournals.permissions@oup.com |
spellingShingle | Original Articles Ferguson, Sherise D Zhou, Shouhao Huse, Jason T de Groot, John F Xiu, Joanne Subramaniam, Deepa S Mehta, Shwetal Gatalica, Zoran Swensen, Jeffrey Sanai, Nader Spetzler, David Heimberger, Amy B Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas |
title | Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas |
title_full | Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas |
title_fullStr | Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas |
title_full_unstemmed | Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas |
title_short | Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas |
title_sort | targetable gene fusions associate with the idh wild-type astrocytic lineage in adult gliomas |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961205/ https://www.ncbi.nlm.nih.gov/pubmed/29718398 http://dx.doi.org/10.1093/jnen/nly022 |
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