Assessment of circulating tumor DNA in cerebrospinal fluid by whole exome sequencing to detect genomic alterations of glioblastoma  

作　　者：Hao Duan Ji-Long Hu Zheng-He Chen Jue-Hui Li Zhen-Qiang He Zhen-Ning Wang Guan-Hua Zhang Xiao-Yu Guo Lun Liang Yong-Gao Mou 

机构地区：[1]Department of Neurosurgery/Neuro-Oncology,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510060,China [2]Department of Abdominal Surgery Oncology,Jiangxi Cancer Hospital,Nanchang,Jiangxi 330029,China

出　　处：《Chinese Medical Journal》2020年第12期1415-1421,共7页中华医学杂志（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.81872324);Science and Technology Planning Project of Guangdong Province,China(No.2018A030313754);Science and Technology Program of Guangzhou,China(Nos.201704020133,201707010169);Science and Technology Planning Project of Jiangmen,China(No.2018630100110019805).

摘　　要：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.

关 键 词：Circulating tumor DNA Cerebrospinal fluid GLIOBLASTOMA Mutation Whole exome sequencing 

分 类 号：R739.41[医药卫生—肿瘤] R730.43[医药卫生—临床医学]