Purpose: TERT promoter mutation (TERTp^Mut) has a strong association to recurrence and has been suggested to act as a driver mutation for malignant transformation of WHO grade I and II meningiomas. TERTp^Mut has been investigated in selected high‐grade meningioma samples. The existence of TERTp^Mut across recurrent tumors in a population‐based cohort needs to be investigated in order to identify when TERTp^Mut emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors. Methods: We gathered material from a consecutive single‐center cohort of 40 patients with malignant meningioma (WHO grade III) treated between 2000 and 2018, including specimens from primary and secondary malignant meningiomas with the corresponding earlier benign specimens and later malignant recurrences. In total 107 tumor samples were studied by Sanger sequencing for TERT promoter mutational status. Results: Seven of 40 patients (17.5%) harbored TERTp^Mut thus validating the incidence of TERTp^Mut in previous non‐population‐based cohorts. In 6/7 patients, the TERTp^Mut was present at initial surgery (WHO grade I–III) while in one patient the TERTp^Mut was found de novo when the meningioma became malignant. The incidences were 2/1.000.000/year for TERTp^Mut WHO grade III meningioma and 8/1.000.000/year for TERTp^wt WHO grade III meningioma in our catchment area. We found a 1.7 times higher recurrence rate (CI 95% 0.65–4.44) and a 2.5 higher mortality rate per 10 person‐years (CI 95% 1.01–6.19) for TERTp^Mut compared to TERTp^wt. Conclusion: TERTp^Mut can occur independently of malignant progression in meningioma and was most often present from the first tumor sample across recurring tumors. TERTp^Mut in WHO grade III may represent a marker of an aggressive subset of tumors.

中文翻译：

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原发性和继发性 WHO III 级脑膜瘤中的 TERT 启动子突变

目的： TERT启动子突变（TERT p ^Mut）与复发有很强的相关性，并被建议作为WHO I级和II级脑膜瘤恶变的驱动突变。已在选定的高级别脑膜瘤样本中研究了TERT p ^Mut。需要对基于人群的队列中复发性肿瘤中TERT p ^Mut的存在进行调查，以确定TERT p ^Mut何时出现在复发性样本中，并验证 WHO III 级肿瘤中的预后影响。方法：我们从 2000 年至 2018 年间接受治疗的 40 名恶性脑膜瘤（WHO III 级）患者的连续单中心队列中收集材料，包括来自原发性和继发性恶性脑膜瘤的标本，以及相应的早期良性标本和晚期恶性复发。通过桑格测序研究了总共 107 个肿瘤样品的TERT启动子突变状态。结果： 40 名患者中有 7 名 (17.5%) 携带TERT p ^Mut，从而验证了先前非基于人群的队列中TERT p ^Mut的发生率。在 6/7 患者中，TERT p ^Mut在初次手术时就出现了（WHO I-III 级），而在一名患者中，当脑膜瘤变成恶性时，从头发现了TERT p ^Mut。在我们的集水区，TERT p ^Mut WHO III 级脑膜瘤的发病率为 2/1.000.000/年，TERT p ^wt WHO III 级脑膜瘤的发病率为8/1.000.000/年。我们发现，与TERT p ^wt相比，TERT p ^{Mut 的}复发率高 1.7 倍（CI 95% 0.65-4.44），每 10 人年死亡率高 2.5（CI 95% 1.01-6.19）。结论：TERT p ^Mut 可以独立于脑膜瘤的恶性进展而发生，并且最常见于复发肿瘤的第一个肿瘤样本。WHO III 级中的TERT p ^Mut可能代表肿瘤侵袭性子集的标志物。