星形胶质瘤和胶质母细胞瘤（GB）是基于中枢神经系统肿瘤第五版世界卫生组织分类的不同异柠檬酸脱氢酶（IDH）突变而被重新分类为成人弥漫性胶质瘤的亚型。胶质瘤的复发是常见且不可避免的挑战，分析星形胶质瘤和GB中的不同基因组变异可能为其进展提供洞见。本研究在65对原发/复发胶质瘤上进行了纵向调查，利用全外显子测序，分析复发过程中染色体臂非整倍体、与癌症相关基因的拷贝数变异（CNVs）和途径富集。通过将我们的数据与多个公共资源整合以及协同免疫组织化学（IHC）确认的方式验证了这些发现的准确性。结果显示，在复发的低等级星形胶质瘤中，非整倍体变化和获得性CNVs的发生率较复发的4级星形胶质瘤和GB要高。更大的非整倍体变化预示着低等级星形胶质瘤的不良预后（P<0.05）。此外，复发时获得性1q、6p得失与低等级星形胶质瘤的整体生存期缩短有关（P<0.05）；然而，这些预后效应局限于4级星形胶质瘤和GB中。而且，在复发过程中6p上12种基因（包括VEGFA）的获得与低等级星形胶质瘤患者的不良预后有关。值得注意的是，复发期间VEGFA表达水平的升高与较差的生存期相符，通过IHC和CGGA数据验证了这一点。总之，这些发现为胶质瘤的进展提供了宝贵的见解，并为指导复发期的治疗方法提供了可能。©2023. Nature Publishing Group UK.

Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence.© 2023. Nature Publishing Group UK.