A Long-term Progression-free Survival with Glioblastoma Patient Harboring MSH6 Pathogenic Germline Mutation: A Case Report

Background 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. LS-related gliomas have poor overall survival. Case presentation We present a case of a31-year-old male patient with a frontal lesion by magnetic resonance imaging (MRI). The pathological diagnosis was isocitrate dehydrogenase (IDH) wildtype glioblastoma (WHO grade 4) with 30% Ki-67 proliferation index. After surgery, this patient received radiotherapy and temozolomide chemotherapy following Stupp protocol. During over 64 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. Conclusion MMR deficiency may lead to TMZ resistance in glioma cells. However, this case had long-term benefits from standard radio- and chemo-therapy 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 glioma patients and the role of microglia in antitumor.