Department of Oncology, The Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA; The Ludwig Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA; The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Department of Neurosurgery, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
Cell Rep Med. 2023 Aug 15;4(8):101148. doi: 10.1016/j.xcrm.2023.101148. Epub 2023 Aug 7.
It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.
利用常规诊断方法，通常难以区分脑部的癌性病变与非癌性病变。我们引入了一种名为 Real-CSF（脑脊液中重复元件非整倍性测序）的分析技术，通过检测脑脊液中的 DNA 来检测中枢神经系统癌症。短散在核元件（SINEs）用单个引物对进行 PCR 扩增，然后通过下一代测序评估 PCR 产物。Real-CSF 评估全基因组拷贝数改变以及选定癌基因的局灶扩增。Real-CSF 应用于 280 例 CSF 样本，正确识别了 184 例癌症患者中的 67%和 96%的 96 例非癌性脑部病变。与同一患者的标准护理细胞学和无浆细胞游离 DNA 分析相比，CSF 分析的灵敏度显著更高。因此，Real-CSF 有能力与其他临床、影像学和基于实验室的资料结合使用，为疑似脑癌患者的诊断和治疗提供信息。
