Targetable gene fusions associate with the IDH wild-type astrocytic lineage in adult gliomas

Sherise D. Ferguson, Shouhao Zhou, Jason T. Huse, John F. de Groot, Joanne Xiu, Deepa S. Subramaniam, Shwetal Mehta, Zoran Gatalica, Jeffrey Swensen, Nader Sanai, David Spetzler, Amy B. Heimberger

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)437-442
Number of pages6
JournalJournal of Neuropathology and Experimental Neurology
Volume77
Issue number6
DOIs
StatePublished - Jun 1 2018

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Gene Fusion
Glioma
Astrocytoma
RNA Sequence Analysis
Oligodendroglioma
Glioblastoma
Oncogenes
Neoplasms
Phosphotransferases
Clinical Trials
Incidence
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Ferguson, S. D., Zhou, S., Huse, J. T., de Groot, J. F., Xiu, J., Subramaniam, D. S., ... Heimberger, A. B. (2018). Targetable gene fusions associate with the IDH wild-type astrocytic lineage in adult gliomas. Journal of Neuropathology and Experimental Neurology, 77(6), 437-442. https://doi.org/10.1093/jnen/nly022
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. In: Journal of Neuropathology and Experimental Neurology. 2018 ; Vol. 77, No. 6. pp. 437-442.
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abstract = "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.",
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Ferguson, SD, Zhou, S, Huse, JT, de Groot, JF, Xiu, J, Subramaniam, DS, Mehta, S, Gatalica, Z, Swensen, J, Sanai, N, Spetzler, D & Heimberger, AB 2018, 'Targetable gene fusions associate with the IDH wild-type astrocytic lineage in adult gliomas', Journal of Neuropathology and Experimental Neurology, vol. 77, no. 6, pp. 437-442. https://doi.org/10.1093/jnen/nly022

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.

In: Journal of Neuropathology and Experimental Neurology, Vol. 77, No. 6, 01.06.2018, p. 437-442.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Targetable gene fusions associate with the IDH wild-type astrocytic lineage in adult gliomas

AU - Ferguson, Sherise D.

AU - Zhou, Shouhao

AU - Huse, Jason T.

AU - de Groot, John F.

AU - Xiu, Joanne

AU - Subramaniam, Deepa S.

AU - Mehta, Shwetal

AU - Gatalica, Zoran

AU - Swensen, Jeffrey

AU - Sanai, Nader

AU - Spetzler, David

AU - Heimberger, Amy B.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

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