PPM1D调控儿童低级别胶质瘤的作用机制及其靶向治疗的可行性研究

分子分型是肿瘤精准医疗的基础。低级别胶质瘤（PLGG）是儿童中枢神经系统最常见的肿瘤，死亡率高达20%，急需进行分子分型。通过多分子分析，我们可将PLGG分为高、中、低风险组（Acta Neuropathologica 2018），但中风险组却找不到特异的标记物，因此仍需寻找新的分子。34例临床标本分析发现PPM1D基因在PLGG中表达异常，与患者预后密切相关，且其能显著影响肿瘤生长。由此推测PPM1D可能是PLGG分型的重要分子。下一步将通过大样本分析，明确其分型价值，并对其影响肿瘤生长的机制做进一步分型。本项目的成功开展可能为PLGG的分子分型提供更有效的标记物，并为靶向治疗提供重要靶点。

Molecular classification is the basis of tumor precise therapy. Low-grade gliomas (LGG) are the most common tumors of the Central Nervous System in children, with a mortality rate of up to 20%, and molecular classification for PLGG is urgently needed. Through multi-molecular analysis, we have successfully used genomic sequencing to stratify PLGG into high-risk group, intermediate-risk group and low-risk group (Acta Neuropathologica 2018), but intermediate-risk group lacks specific molecular markers. 34 PLGGs have been found PPM1D gene appears abnormally, these patients showed poor clinical outcome and it can significantly affect tumor growth. We hypothesis that PPM1D may act as a prognostic biomarker of PLGG. We will further to clarify its molecular classification value via large clinical cohort and its mechanism that affects tumor growth. This project aims to provide novel understandings of molecular classification of PLGG, and important target for targeted therapy.