TERT Alterations Predict Tumor Progression in De Novo High-Grade Meningiomas Following Adjuvant Radiotherapy.
TERT Alterations Predict Tumor Progression in De Novo High-Grade Meningiomas Following Adjuvant Radiotherapy.
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DOI：
10.3389/fonc.2021.747592
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发表时间：
2021
影响因子：
4.7
通讯作者：
Gong Y
中科院分区：
文献类型：
--
作者：
Deng J;Sun S;Chen J;Wang D;Cheng H;Chen H;Xie Q;Hua L;Gong Y
辅助放疗 (RT) 是手术后新发高级别脑膜瘤 (HGM) 最常用的治疗方法之一，但临床获益的遗传决定因素尚不清楚。我们描述了整合临床基因组学以发现预测生物标志物的努力，这些生物标志物将为从头 HGM 中的辅助治疗决策提供信息。我们对 37 名放疗后重新出现 HGM 的患者进行了回顾性分析。在所有病例中均进行了涵盖 184 个基因的基于临床杂交捕获的测序测定。评估了肿瘤临床/基因组特征与 RT 反应之间的关联。使用 Kaplan-Meier 方法绘制总生存期 (OS) 和无进展生存期 (PFS) 曲线。在来自同一机构的 172 例 HGM 中，42 例（37 例 WHO 2 级脑膜瘤和 5 例 WHO 3 级脑膜瘤）在放疗后被确定为新发 HGM。仅 TERT 突变 [62.5% C228T； 25%C250T； 12.5% 拷贝数扩增 (CN amp.)] 与术后 RT 后肿瘤进展显着相关（调整后的 p = 0.003）。 TERT 和其他测试基因之间潜在的不同体细胞相互作用尚未确定。此外，TERT 改变 (TERT-alt) 是肿瘤进展的预测因子（Fisher 精确检验，p = 0.003），并且与 RT 后新 HGM 中 PFS 降低（对数秩检验，p = 0.0114）相关。我们的研究结果表明，TERT-alt 与新诊断的 HGM 患者术后 RT 后的肿瘤进展和不良预后相关。
Adjuvant radiotherapy (RT) is one of the most commonly used treatments for de novo high-grade meningiomas (HGMs) after surgery, but genetic determinants of clinical benefit are poorly characterized. We describe efforts to integrate clinical genomics to discover predictive biomarkers that would inform adjuvant treatment decisions in de novo HGMs. We undertook a retrospective analysis of 37 patients with de novo HGMs following RT. Clinical hybrid capture-based sequencing assay covering 184 genes was performed in all cases. Associations between tumor clinical/genomic characteristics and RT response were assessed. Overall survival (OS) and progression-free survival (PFS) curves were plotted using the Kaplan–Meier method. Among the 172 HGMs from a single institution, 42 cases (37 WHO grade 2 meningiomas and five WHO grade 3 meningiomas) were identified as de novo HGMs following RT. Only TERT mutations [62.5% C228T; 25% C250T; 12.5% copy number amplification (CN amp.)] were significantly associated with tumor progression after postoperative RT (adjusted p = 0.003). Potential different somatic interactions between TERT and other tested genes were not identified. Furthermore, TERT alterations (TERT-alt) were the predictor of tumor progression (Fisher’s exact tests, p = 0.003) and were associated with decreased PFS (log-rank test, p = 0.0114) in de novo HGMs after RT. Our findings suggest that TERT-alt is associated with tumor progression and poor outcome of newly diagnosed HGM patients after postoperative RT.
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影响因子：
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作者：
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