Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas
Targetable Gene Fusions Associate With the IDH Wild-Type Astrocytic Lineage in Adult Gliomas
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DOI：
10.1093/jnen/nly022
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发表时间：
2018-06-01
影响因子：
3.2
通讯作者：
Heimberger, Amy B.
中科院分区：
文献类型：
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作者：
Ferguson, Sherise D.;Zhou, Shouhao;Heimberger, Amy B.
基因融合涉及癌基因已被报道在胶质瘤，并可能作为新的治疗靶点。使用RNA测序，我们询问了一个大的胶质瘤队列，以评估靶向基因融合的发生率。使用ArcherDx融合蛋白测定分析神经胶质瘤（n = 390）。五十二个基因的目标进行了分析，并与保存激酶结构域的融合进行了研究。总体而言，36例胶质瘤（9%）共包含37例潜在靶向融合，其中大多数见于星形细胞瘤（n = 34）。在该谱系中，11%（25/235）的胶质母细胞瘤、12%（5/42）的间变性星形细胞瘤、8%（2/25）的II级星形细胞瘤和33%（2/6）的毛细胞性星形细胞瘤具有靶向融合。相对于IDH突变体（4%; n = 4/109），融合在IDH野生型肿瘤（12%，n = 31/261）中显著更频繁（p = 0.011）。在少突胶质细胞瘤中未观察到融合。最常观察到的治疗靶向融合是FGFR（n = 12）、MET（n = 11）和NTRK（n = 8）。在神经胶质瘤中发现了几种以前没有描述过的新融合，包括EGFR：VWC 2和FGFR 3：NBR 1。总之，可靶向基因融合在IDH野生型高级别星形细胞肿瘤中富集，这将影响神经胶质瘤患者临床试验的招募和解释。
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.