Department of Pathology, University of Health Sciences Gaziosmanpasa Research and Training Hospital, ISTANBUL, TURKEY.
Turk Patoloji Derg. 2022;38(2):90-98. doi: 10.5146/tjpath.2021.01555.
Diffuse gliomas, the most common primary malignant brain tumors, have been classified by the World Health Organization as class II-IV gliomas. After 2016, two mutations in the promoter region of the telomerase reverse transcriptase (TERT) gene were identified in addition to the IDH, 1p / 19q, and ATRX status.
We identified 84 patients with grade II-IV glioma with IDH, ATRX, 1p / 19q and TERT status. All tumor samples were subjected to molecular genetic screening (Sanger sequencing for IDH and TERT mutations, fluorescence in situ hybridization for 1p/19q status) after histological diagnosis (immunohistochemistry for IDH1 R132H, ATRX, and p53) for a more precise molecular diagnosis. The confidence intervals were calculated at the 95% confidence level, and differences at p < 0.05 were considered statistically significant.
Primary glioblastomas had the highest frequency of TERT promoter mutations (25 of 28, 89.2%, p=0.006) followed by oligodendrogliomas (29 of 35, 82.8%, p < 0.001) while astrocytomas showed the lowest frequency (3 of 15, 20%, p=0.107), and the positivity significantly differed among these three groups (p < 0.001). TERT promoter mutations were more frequent in patients older than 55 years of age at diagnosis (p=0.023). The group with TERT promoter mutations, and without IDH mutations showed the worst overall survival. However, the presence of both TERT promoter and IDH mutations, which resembled oligodendroglial progression, showed best overall survival (p=0.042).
The discovery of TERT promoter mutations in numerous gliomas has opened the door for a better molecular classification of gliomas, and TERT status is associated with survival. Further studies will help in elucidating the value of TERT promoter mutations as biomarkers in clinical practice, and eventual therapeutic targets.
弥漫性神经胶质瘤是最常见的原发性恶性脑肿瘤，被世界卫生组织（World Health Organization）归类为 II-IV 级神经胶质瘤。继 2016 年之后，除 IDH、1p/19q 和 ATRX 状态外，又在端粒酶逆转录酶（TERT）基因启动子区发现了两种突变。
我们鉴定了 84 例 IDH、ATRX、1p/19q 和 TERT 状态的 II-IV 级神经胶质瘤患者。在组织学诊断（IDH1 R132H、ATRX 和 p53 的免疫组织化学）后，所有肿瘤样本均进行了分子遗传学筛查（IDH 和 TERT 突变的 Sanger 测序，1p/19q 状态的荧光原位杂交），以进行更精确的分子诊断。置信区间计算在 95%置信水平，p<0.05 差异具有统计学意义。
原发性胶质母细胞瘤的 TERT 启动子突变频率最高（28 例中的 25 例，89.2%，p=0.006），其次是少突胶质细胞瘤（35 例中的 29 例，82.8%，p<0.001），而星形细胞瘤的频率最低（15 例中的 3 例，20%，p=0.107），这三组之间的阳性率差异具有统计学意义（p<0.001）。TERT 启动子突变在诊断时年龄大于 55 岁的患者中更为常见（p=0.023）。存在 TERT 启动子突变而无 IDH 突变的患者总生存期最差。然而，存在 TERT 启动子和 IDH 突变的患者，类似于少突胶质细胞进展，总生存期最佳（p=0.042）。
在许多神经胶质瘤中发现 TERT 启动子突变，为神经胶质瘤的更好分子分类开辟了道路，TERT 状态与生存相关。进一步的研究将有助于阐明 TERT 启动子突变作为临床实践中的生物标志物的价值，并最终成为治疗靶点。
