Zhou Yiqiang, Duan Qianqian, Han Tiantian, Piao Yueshan, Tang Jie
Department of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute (CHINA-INI), Capital Medical University, National Center for Neurological Disorders, Beijing, China.
State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd., Nanjing, China.
Discov Oncol. 2025 Aug 6;16(1):1481. doi: 10.1007/s12672-025-03361-x.
Lynch syndrome (LS) is a cancer syndrome caused by germline mutations in DNA mismatch repair genes. Patients with Lynch syndrome have higher risk of brain tumors, predominantly high-grade gliomas, including glioblastoma (GBM). Here, we present a case of a 31-year-old male patient with a frontal lesion by magnetic resonance imaging (MRI). The pathological diagnosis was isocitrate dehydrogenase (IDH) wildtype GBM (WHO grade 4) with 30% Ki-67 proliferation index. After surgery, this patient received radiotherapy and temozolomide chemotherapy following Stupp protocol. During over 60 months follow up, no sign of tumor recurrence was found after surgery. Therefore, next-generation sequencing was suggested to this patient. The result revealed a heterozygous germline variation of c.3261dup in exon 5 of MSH6 gene which resulted in a truncated MSH6 protein (MSH6 p.F1088Lfs*5) with a tumor mutation burden of 327.36 Mut/Mb. MMR deficiency may usually lead to TMZ resistance in GBM cells. However, this case had long-term benefits from standard Stupp protocol after surgery, probably due to the distinct molecular characteristics and tumor microenvironment. This finding provided insight to perform clinical studies to investigate the molecular characterization of Lynch associated GBM and the role of microglia in antitumor.
林奇综合征（LS）是一种由DNA错配修复基因种系突变引起的癌症综合征。林奇综合征患者患脑肿瘤的风险更高，主要是高级别胶质瘤，包括胶质母细胞瘤（GBM）。在此，我们报告一例31岁男性患者，通过磁共振成像（MRI）发现额叶有病变。病理诊断为异柠檬酸脱氢酶（IDH）野生型GBM（世界卫生组织4级）且Ki-67增殖指数为30%。手术后，该患者按照Stupp方案接受了放疗和替莫唑胺化疗。在超过60个月的随访中，术后未发现肿瘤复发迹象。因此，建议对该患者进行二代测序。结果显示MSH6基因第5外显子存在c.3261dup杂合种系变异，导致MSH6蛋白截短（MSH6 p.F1088Lfs*5），肿瘤突变负荷为327.36 Mut/Mb。错配修复缺陷通常可能导致GBM细胞对替莫唑胺耐药。然而，该病例术后从标准Stupp方案中获得了长期益处，可能是由于独特的分子特征和肿瘤微环境。这一发现为开展临床研究以探究林奇相关GBM的分子特征以及小胶质细胞在抗肿瘤中的作用提供了思路。
