成年人的组织学低级星形细胞瘤（LGAs）根据异柠檬酸脱氢酶（IDH）基因的突变状态进行分类。野生型（WT）LGAs通常很快发展为胶质母细胞瘤（GBM），而突变肿瘤通常会呈缓慢进展。为了找到可能影响不同行为的因素，我们比较了它们各自的转录组。与突变型LGAs不同，血小板源性生长因子（PDGF）信号在WT肿瘤中显著富集，而PDGFA是该通路中最高的过度表达基因。此外，PDGFA和PDGFD启动子的甲基化出现为突变型肿瘤中的低表达提供可能机制。基因拷贝数增加的7号染色体与WT病例中PDGFA的高表达同时出现，而高水平的PDGFA表达与异倍体、细胞外基质（ECM）相关的免疫抑制特征和不良预后相关。我们还注意到，WT病例中的高PDGFA表达与肿瘤等级无关，并且在PDGFA过表达肿瘤的进展中 Begind：出现多种p53通路失活机制。相反，TP53点突变是突变型LGAs的早期和恒定特征。我们的结果表明，PDGF基因家族的成员，与不同的p53通路改变一起，是LGA行为的基础。 ©2023作者（S）。

Diffuse, histologically lower grade astrocytomas of adults (LGAs) are classified based on the mutational status of the isocitrate dehydrogenase (IDH) genes. While wild-type (WT) LGAs often evolve quickly to glioblastoma (GBM), mutant tumors typically follow an indolent course. To find possible effectors of these different behaviors, we compared their respective transcriptomes. Unlike mutant LGAs, platelet-derived growth factor (PDGF) signaling was significantly enriched in WT tumors, and PDGFA was the top overexpressed gene in the pathway. Moreover, methylation of the PDGFA and PDGFD promoters emerged as a possible mechanism for their low expression in mutant tumors. Copy number gain of chromosome 7 co-occurred with high expression of PDGFA in WT cases, and high expression of PDGFA was associated with aneuploidy, extracellular matrix (ECM)-related immunosuppressive features and poor prognosis. We also noted that high PDGFA expression in WT cases occurred irrespective of tumor grade and that multiple mechanisms of p53 pathway inactivation accompanied progression to GBM in PDGFA-overexpressing tumors. Conversely, TP53 point mutations were an early and constant feature of mutant LGAs. Our results suggest that members of the PDGF gene family, in concert with different p53 pathway alterations, underlie LGA behaviors.© 2023. The Author(s).