Chen Zirong, Yang Huaitao, Wang Jiajia, Long Guoxian, Xi Qingsong, Chen Tao, He Yue, Zhang Bin, Wan Feng
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Neurosurgery, Jingzhou Central Hospital, Jingzhou, China.
Front Neurol. 2023 Apr 27;14:1148848. doi: 10.3389/fneur.2023.1148848. eCollection 2023.
Single recurrence in the sub-frontal region after cerebellar medulloblastoma (MB) resection is rare and the underlying molecular characteristics have not been specifically addressed.
We summarized two such cases in our center. All five samples were molecularly profiled for their genome and transcriptome signatures.
The recurrent tumors displayed genomic and transcriptomic divergence. Pathway analysis of recurrent tumors showed functional convergence in metabolism, cancer, neuroactive ligand-receptor interaction, and PI3K-AKT signaling pathways. Notably, the sub-frontal recurrent tumors had a much higher proportion (50-86%) of acquired driver mutations than that reported in other recurrent locations. The acquired putative driver genes in the sub-frontal recurrent tumors functionally enriched for chromatin remodeler-associated genes, such as KDM6B, SPEN, CHD4, and CHD7. Furthermore, the germline mutations of our cases showed a significant functional convergence in focal adhesion, cell adhesion molecules, and ECM-receptor interaction. Evolutionary analysis showed that the recurrence could be derived from a single primary tumor lineage or had an intermediate phylogenetic similarity to the matched primary one.
Rare single sub-frontal recurrent MBs presented specific mutation signatures that might be related to the under-dose radiation. Particular attention should be paid to optimally covering the sub-frontal cribriform plate during postoperative radiotherapy targeting.
小脑髓母细胞瘤（MB）切除术后额叶下区域单发复发罕见，其潜在分子特征尚未得到具体研究。
我们总结了本中心的两例此类病例。对所有五个样本进行了基因组和转录组特征的分子分析。
复发肿瘤显示出基因组和转录组的差异。复发肿瘤的通路分析显示在代谢、癌症、神经活性配体-受体相互作用和PI3K-AKT信号通路中存在功能趋同。值得注意的是，额叶下复发肿瘤获得性驱动突变的比例（50-86%）远高于其他复发部位的报道。额叶下复发肿瘤中获得的假定驱动基因在功能上富集于染色质重塑相关基因，如KDM6B、SPEN、CHD4和CHD7。此外，我们病例的种系突变在粘着斑、细胞粘附分子和ECM-受体相互作用方面显示出显著的功能趋同。进化分析表明，复发可能源自单一原发肿瘤谱系，或与匹配的原发肿瘤具有中间系统发育相似性。
罕见的额叶下单发复发MB呈现出可能与放疗剂量不足相关的特定突变特征。在术后放疗定位时，应特别注意最佳覆盖额叶下筛板。
