H3K27M突变型脑干胶质瘤（Brainstem glioma with H3K27M mutation, BSG-H3K27M），是儿童因为脑肿瘤死亡的首要原因，中位生存期仅9-12个月。放疗为其标准治疗方案，然而几乎所患者均会复发/进展。复发/进展时的治疗方案依然建立在放疗前组织或分子病理诊断的基础上，导致大多数后续治疗无效，因此明确放疗后肿瘤发生的分子演变对于有针对性地设计后续治疗方案具有重要意义。然而，由于脑干解剖位置极其重要，无法反复进行手术或活检，因此通过多次组织测序解决该问题不具备可行性。本人前期研究显示脑脊液ctDNA可以忠实地反映肿瘤组织的突变信息，敏感性达到97.1%。本课题拟通过对脑脊液ctDNA深度测序从基因突变层面揭示BSG-H3 K27M放疗前后的分子演变，深化人们对于放疗后复发BSG-H3 K27M的认识，为将来设计针对性的治疗方案和临床试验等提供理论支持。

Brainstem glioma with H3K27M mutation (BSG-H3K27M) is the leading cause of brain tumor-related death in children, with a median overall survival of 9-12 months. Radiotherapy is the standard care of treatment for BSG-H3K27M, although it can only offer transient tumor control, and nearly all patients will experience tumor recurrence/progression, most of which occur within 3-6 months after radiotherapy. Currently, treatment strategies for recurrent or progressive tumors are still based on pre-treatment initial histopathological or molecular pathologic diagnosis, which is the major cause of failure for these strategies. Therefore, illuminating the mutational changes of tumors subsequent to radiotherapy is critical for designing corresponding treatment strategies. However, due to the eloquence of the brainstem, it is impossible to address this question via serial tumor tissue sequencing. Recently, we have proved that cerebrospinal fluid (CSF)-derived ctDNA can faithfully recapitulate tumor mutational profile, with a sensitivity of 97.1%. Here, we aim to leverage this technique to investigate the mutational change of BSG-H3K27M after radiotherapy, providing an insightful understanding of recurrent BSG-H3K27M tumors. Solving these questions will help optimize strategies and the design of clinical trials for BSG-H3K27M on recurrence/progression in the future.