Mutation in the telomerase reverse transcriptase promoter (TERTp)is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, includingTERTpmutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan–Meier survival and Cox regression analysis.TERTpmutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2),TERTpmutations emerged as a significant adverse prognostic factor (p= 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence ofTERTpmutations did not significantly impact patient prognosis (p= 0.215 and 0.268, respectively). Due to the high frequency ofTERTpmutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When consideringMGMTpstatus, the combinedTERTp-mutated andMGMTp-unmethylated group exhibited the worst prognosis in OS (p= 0.018) and PFS (p= 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age,MGMTpmethylation, andCDKN2A/Bhomozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index andMYCNamplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas.
端粒酶逆转录酶启动子（TERTp）突变常见于多种恶性肿瘤，如中枢神经系统（CNS）肿瘤、恶性黑色素瘤、膀胱癌和甲状腺癌。这些突变被认为是这些肿瘤的重要不良预后因素。本研究根据2021年第五版世界卫生组织（WHO）中枢神经系统肿瘤分类标准（WHO2021），对单中心诊断的528例成人型弥漫性胶质瘤病例进行了重新分类。研究分析了各肿瘤的临床病理学特征和遗传学特征，包括TERTp突变。通过Kaplan-Meier生存分析和Cox回归分析，评估了已知预后因素对患者结局的影响。TERTp突变在94.1%的少突胶质细胞瘤（ODG）中被检出，其次为66.3%的IDH野生型胶质母细胞瘤（GBM-IDHwt），以及9.2%的IDH突变型星形细胞瘤（A-IDHm）。当将A-IDHm和GBM视为星形细胞肿瘤（第1组），ODG视为第2组时，TERTp突变成为第1组中显著的不良预后因素（p=0.013）。然而，在GBM-IDHwt和A-IDHm各自内部，TERTp突变的存在并未显著影响患者预后（p值分别为0.215和0.268）。由于第2组（ODG）中TERTp突变频率极高且患者生存期普遍较长，评估其对总生存期影响的统计分析被认为不切实际。在考虑MGMTp状态时，TERTp突变合并MGMTp非甲基化组在GBM的总生存期（OS，p=0.018）和无进展生存期（PFS，p=0.034）方面预后最差。本研究证实，根据WHO2021标准进行的肿瘤分类能有效反映预后。在GBM中，单变量和多变量分析均显示年龄、MGMTp甲基化和CDKN2A/B纯合缺失是具有统计学意义的预后因素；而在A-IDHm的单变量分析中，4级、Ki-67指数和MYCN扩增是具有统计学意义的预后因素。本研究提示，在成人型弥漫性胶质瘤中，根据遗传学特征对肿瘤进行分类和管理至关重要。
Prognostic Impact ofTERTPromoter Mutations in Adult-Type Diffuse Gliomas Based on WHO2021 Criteria
肿瘤(癌症)患者之家