Department of Neurosurgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Pathology, Center of Diagnostic Investigation, Copenhagen University Hospital, Copenhagen, Denmark.
Brain Pathol. 2021 Jan;31(1):61-69. doi: 10.1111/bpa.12892. Epub 2020 Sep 15.
TERT promoter mutation (TERTp ) 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 has been investigated in selected high-grade meningioma samples. The existence of TERTp across recurrent tumors in a population-based cohort needs to be investigated in order to identify when TERTp emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors.
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.
Seven of 40 patients (17.5%) harbored TERTp thus validating the incidence of TERTp in previous non-population-based cohorts. In 6/7 patients, the TERTp was present at initial surgery (WHO grade I-III) while in one patient the TERTp was found de novo when the meningioma became malignant. The incidences were 2/1.000.000/year for TERTp WHO grade III meningioma and 8/1.000.000/year for TERTp 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 compared to TERTp .
TERTp can occur independently of malignant progression in meningioma and was most often present from the first tumor sample across recurring tumors. TERTp in WHO grade III may represent a marker of an aggressive subset of tumors.
端粒酶逆转录酶启动子突变（TERTp）与复发有很强的关联，并被认为是 WHO 分级 I 和 II 级脑膜瘤恶性转化的驱动突变。TERTp 已在选定的高级别脑膜瘤样本中进行了研究。为了确定 TERTp 在复发性肿瘤中的出现时间，并验证其在 WHO 分级 III 肿瘤中的预后影响，需要在基于人群的队列中研究 TERTp 在复发性肿瘤中的存在情况。
我们收集了 2000 年至 2018 年间连续单中心队列的 40 例恶性脑膜瘤（WHO 分级 III）患者的材料，包括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标本。总共对 107 个肿瘤样本进行了 Sanger 测序，以检测 TERT 启动子突变状态。
40 例患者中有 7 例（17.5%）存在 TERTp，这验证了 TERTp 在以前非基于人群的队列中的发生率。在 6/7 例患者中，TERTp 存在于初次手术时（WHO 分级 I-III），而在 1 例患者中，当脑膜瘤恶变时，发现 TERTp 是新出现的。TERTp WHO 分级 III 脑膜瘤的发生率为 2/1000000/年，TERTp WHO 分级 III 脑膜瘤在我们的集水区的发生率为 8/1000000/年。我们发现 TERTp 组的复发率（95%CI 0.65-4.44）高 1.7 倍，每 10 人年的死亡率（95%CI 1.01-6.19）高 2.5 倍。
TERTp 可独立于脑膜瘤的恶性进展而发生，且最常存在于复发性肿瘤的首个肿瘤样本中。WHO 分级 III 中的 TERTp 可能代表肿瘤侵袭性亚群的标志物。
