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.
N1 - Funding Information:
Send correspondence to: Sherise D. Ferguson, MD, Department of Neurosur-gery, The University of Texas MD Anderson Cancer Center, 1400 Hol-combe Blvd., Houston, TX 77030; E-mail: sdferguson@mdanderson.org This research was funded by the Dr. Marnie Rose Foundation and the Na-tional Institutes of Health (CA 1208113, P50 CA127001, P30 CA016672).
Publisher Copyright:
© 2018 American Association of Neuropathologists, Inc.
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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U2 - 10.1093/jnen/nly022
DO - 10.1093/jnen/nly022
M3 - Article
C2 - 29718398
AN - SCOPUS:85048575785
SN - 0022-3069
VL - 77
SP - 437
EP - 442
JO - Journal of neuropathology and experimental neurology
JF - Journal of neuropathology and experimental neurology
IS - 6
ER -