高级成人型弥漫性胶质瘤（HGGs）是一组异质的侵袭性肿瘤，大多数不可治愈。近期的进展突显了核糖体在癌症发展中的贡献，为临床提供了新的视角。本研究发现IDHwt和IDHmut HGGs在核糖体生物学方面存在明显差异，包括rRNA表观转录组学和核糖体生物发生学方面的变化，这可能构成新的特征，可用于这些病理学的管理。我们采用RiboMethSeq和本实验组开发的生物信息学工具（h t t p s : //github.com/RibosomeCRCL/ribomethseq-nfandrRMSAnalyzer）对三个独立组合的71个HGG（IDHwt n=30，IDHmut n=41）和9个非肿瘤样本进行了（i）核糖体RNA 2'O-核糖甲基化（rRNA 2'Ome）分析，（ii）中通量RT-qPCR分析核糖体生物发生因子的表达，以作为核糖体生物发生的指标，以及（iii）对5种HGG细胞系对RNA Pol I抑制剂（CX5461，BMH21）的敏感性进行了分析。非监督分析显示，根据rRNA 2'Ome表观转录组学特征，HGGs能够区分开来，其中IDHwt型胶质母细胞瘤在特定位点的rRNA 2'Ome变化最显著。相反，与非肿瘤组织或IDHwt型胶质母细胞瘤相比，IDHmut HGGs主要表现为核糖体生物发生因子的过度表达。最后，IDHmut HGG来源的球体对CX5461的细胞毒性更高，而所有HGG球体对BMH-21的细胞毒性相似。在HGGs中，IDH突变状态与核糖体生物学的特定变化以及对RNA Pol I抑制剂的不同敏感性相关。© 作者（们）2023年。由牛津大学出版社代表神经肿瘤学会出版。版权所有。有关权限，请发送电子邮件至：journals.permissions@oup.com。

High-grade adult-type diffuse gliomas (HGGs) constitute a heterogeneous group of aggressive tumors that are mostly incurable. Recent advances highlighting the contribution of ribosomes to cancer development have offered new clinical perspectives. Here, we uncovered that IDHwt and IDHmut HGGs display distinct alterations of ribosome biology, in terms of rRNA epitranscriptomics and ribosome biogenesis, which could constitute novel hallmarks that can be exploited for the management of these pathologies.We analyzed (i) the ribosomal RNA 2'O-ribose methylation (rRNA 2'Ome) using RiboMethSeq and in-house developed bioinformatics tools (h t t p s : //github.com/RibosomeCRCL/ribomethseq-nfandrRMSAnalyzer) on three independent cohorts compiling 71 HGGs (IDHwt n=30, IDHmut n=41) and 9 non-neoplastic samples, (ii) the expression of ribosome biogenesis factors using medium throughput RT-qPCR as a readout of ribosome biogenesis, and (iii) the sensitivity of 5 HGG cell lines to RNA Pol I inhibitors (CX5461, BMH21).Unsupervised analysis demonstrated that HGGs could be distinguished based on their rRNA 2'Ome epitranscriptomic profile, with IDHwt glioblastomas displaying the most significant alterations of rRNA 2'Ome at specific sites. In contrast, IDHmut HGGs are largely characterized by an overexpression of ribosome biogenesis factors compared to non-neoplastic tissues or IDHwt glioblastomas. Finally, IDHmut HGG-derived spheroids display higher cytotoxicity to CX5461 than IDHwt glioblastoma, while all HGG spheroids display a similar cytotoxicity to BMH-21.In HGGs, IDH mutational status is associated with specific alterations of the ribosome biology and with distinct sensitivities to RNA Pol I inhibitors.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.