Assessment of circulating tumor DNA in cerebrospinal fluid by whole exome sequencing to detect genomic alterations of glioblastoma / 中华医学杂志(英文版)

BACKGROUND@#Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma.@*METHODS@#CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared.@*RESULTS@#Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF compared with the corresponding tumor tissue samples (3.56 ± 0.75 vs. 2.22 ± 0.32, P = 0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.1% ± 6.0% vs. 73.8% ± 6.0%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3 histone, family 3A (H3F3A) which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF.@*CONCLUSION@#Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

Research Progress of Glioma Immunotherapy / 中山大学学报(医学科学版)

@#Gliomas are the most common primary malignant tumors in the central nervous system，and more than half of them are WHO grade IV glioblastomas. Even if surgery，concurrent chemoradiotherapy and adjuvant chemotherapy were applied，median survival of GBM patients is still only 14.2 months. Immunosuppression is an important feature of malignant glioma. Immunotherapy which reverse immunosuppression may be the most promising way to improve the treatment effect of glioma patients in recent years. This article reviews the recent progress of glioma immunotherapy and the research progress of regulatory T cells（Treg）and glucocorticoid-induced tumor necrosis factor receptor（GITR）in the glioma microenvironment. We hope this article will provides new research ideas for glioma immunotherapy.