神经胶质瘤（glioma）远程复发的基因组改变的进化轨迹大部分尚未知晓。为了阐明神经胶质瘤的进化，我们基于深度全基因组测序数据（ctDNA），分析了原发肿瘤和复发肿瘤或原位肿瘤液（TISF）的配对样本的进化轨迹。我们发现，在IDH突变的神经胶质瘤中，MMR基因突变发生在基因进化的后期，激活多条信号通路并显著增加了远程复发的潜力。PDGFRA扩增特征的偏向神经胶质瘤亚型可能易于在治疗后发生高突变性和远程复发。经典和间质亚型往往通过亚克隆重构、主干基因转换和收敛进化进行局部进展。EGFR和NOTCH信号通路以及CDNK2A突变在促进肿瘤局部进展中起重要作用。神经胶质瘤亚型显示出不同的首选进化模式。ClinicalTrials.gov，NCT05512325。©2023 作者。

The evolutionary trajectories of genomic alterations underlying distant recurrence in glioma remain largely unknown. To elucidate glioma evolution, we analyzed the evolutionary trajectories of matched pairs of primary tumors and relapse tumors or tumor in situ fluid (TISF) based on deep whole-genome sequencing data (ctDNA). We found that MMR gene mutations occurred in the late stage in IDH-mutant glioma during gene evolution, which activates multiple signaling pathways and significantly increases distant recurrence potential. The proneural subtype characterized by PDGFRA amplification was likely prone to hypermutation and distant recurrence following treatment. The classical and mesenchymal subtypes tended to progress locally through subclonal reconstruction, trunk genes transformation, and convergence evolution. EGFR and NOTCH signaling pathways and CDNK2A mutation play an important role in promoting tumor local progression. Glioma subtypes displayed distinct preferred evolutionary patterns. ClinicalTrials.gov, NCT05512325.© 2023 The Author(s).