文章：

与C228T突变相比，C250T突变对端粒和染色体的生物学影响较小，可能为胶质母细胞瘤患者带来更好的预后。

The C250T Mutation ofTERTpMight Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation

原文发布日期：9 February 2024

DOI: 10.3390/cancers16040735

类型: Article

开放获取: 是

英文摘要：

The aim of this study was to determine howTERTpmutations impact glioblastoma prognosis. Materials and Methods:TERTpmutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients. Results: Overall, there were no differences in outcomes between patients with mutatedTERTp-wt orTERTp. However, we found significant differences according to the type ofTERTpmutation. Progression-free survival (mPFS) was 9.1 months for those with the C250T mutation and 7 months for those with either the C228T mutation orTERTp-wt (p= 0.016). Overall survival (mOS) was 21.9 and 15 months, respectively (p= 0.026). This differential effect was more pronounced in patients withMGMTpmethylation (mPFS:p= 0.008; mOS:p= 0.021). Multivariate analysis identified the C250T mutation as an independent prognostic factor for longer mOS (HR 0.69;p= 0.044). We found no differences according toTERTpmutation status in molecular alterations common in glioblastoma, nor in copy number variants in genes related to alternative lengthening of telomeres. Nevertheless, in the gene enrichment analysis adjusted forMGMTpmethylation status, some Reactome gene sets were differentially enriched, suggesting that the C250T mutation may exert a lesser effect on telomeres or chromosomes. Conclusions: In our series, patients exhibiting the C250T mutation had a more favorable prognosis compared to those with eitherTERPp-wt orTERTpC228T mutations. Additionally, our findings suggest a reduced involvement of the C250T mutation in the underlying biological mechanisms related to telomeres.

摘要翻译： 

本研究旨在探讨TERTp突变对胶质母细胞瘤预后的影响。材料与方法：回顾性分析258例接受统一治疗的胶质母细胞瘤患者，检测其TERTp突变状态。部分患者可获得RNA测序和全外显子组测序数据。结果：总体而言，TERTp突变型与野生型患者的预后无显著差异。但根据TERTp突变类型分析发现显著差异：携带C250T突变者的无进展生存期（mPFS）为9.1个月，而C228T突变或TERTp野生型患者为7个月（p=0.016）；总生存期（mOS）分别为21.9个月和15个月（p=0.026）。这种差异在MGMTp甲基化患者中更为显著（mPFS：p=0.008；mOS：p=0.021）。多变量分析显示C250T突变是延长mOS的独立预后因素（HR 0.69；p=0.044）。在胶质母细胞瘤常见分子改变及端粒替代延长相关基因拷贝数变异方面，不同TERTp突变状态未显示差异。然而，经MGMTp甲基化状态校正的基因富集分析显示，部分Reactome基因集存在差异富集，提示C250T突变可能对端粒或染色体影响较弱。结论：本研究中，携带C250T突变的患者较TERTp野生型或C228T突变者预后更佳。此外，研究提示C250T突变在端粒相关生物学机制中的参与程度可能较低。

原文链接：

The C250T Mutation ofTERTpMight Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation