Aulakh Sonikpreet, Xiu Joanne, Hinton Andrew, Darabi Sourat, Demeure Michael J, Sengupta Soma, Kesari Santosh, Ashley David M, Sumrall Ashley Love, Glantz Michael J, Spetzler David
West Virginia University, Morgantown, West Virginia, USA.
Caris Life Sciences, Medical Affairs, Phoenix, Arizona, USA.
Neurooncol Adv. 2024 Oct 4;6(1):vdae169. doi: 10.1093/noajnl/vdae169. eCollection 2024 Jan-Dec.
High-grade gliomas (HGGs) are the most aggressive type of gliomas and have the poorest outcomes. Chromatin remodeling (CR) genes have been implicated in multiple oncogenic pathways in numerous cancer types. In gliomagenesis, CR genes have been implicated in regulating the stemness of glioma cells, the tumor microenvironment (TME), and resistance to therapies.
We performed molecular profiling of 4244 HGGs and evaluated associations of CR mutations with other cancer-related biomarkers, infiltration by immune cells, and immune gene expression. We also evaluated the association between CR mutations and survival in wild-type HGG patients.
Nearly 10% of HGGs carry mutations in CR genes, with a higher prevalence (15%) in HGGs with mutations. Analysis of cooccurrence with other biomarkers revealed that CR-mutated HGGs possess favorable genetic alterations which may have prognostic value. CR-mutated HGGs with wild-type demonstrated colder TME and worse OS overall compared to the CR-wild-type HGGs.
Our study reveals the prognostic effects of CR mutations in HGG and points to several biomarker candidates that could suggest sensitivity to emerging therapeutic strategies.
高级别胶质瘤（HGGs）是最具侵袭性的胶质瘤类型，预后最差。染色质重塑（CR）基因与多种癌症类型的多个致癌途径有关。在胶质瘤发生过程中，CR基因与调节胶质瘤细胞的干性、肿瘤微环境（TME）以及对治疗的抗性有关。
我们对4244例HGGs进行了分子分析，并评估了CR突变与其他癌症相关生物标志物、免疫细胞浸润和免疫基因表达的关联。我们还评估了CR突变与野生型HGG患者生存之间的关联。
近10%的HGGs携带CR基因突变，在有突变的HGGs中患病率更高（15%）。与其他生物标志物共现分析显示，CR突变的HGGs具有可能具有预后价值的有利基因改变。与CR野生型HGGs相比，野生型CR突变的HGGs表现出更冷的TME和总体更差的总生存期（OS）。
我们的研究揭示了CR突变在HGG中的预后作用，并指出了几个可能提示对新兴治疗策略敏感性的生物标志物候选物。
