Cell-free tumor DNA in cerebral spinal fluid decodes tumors of the central nervous system

 描述(申请人提供)：我们正在开发一种创新的、微创的方法来研究转移性和原发于中枢神经系统(CNS)的肿瘤的遗传谱。细胞游离DNA(CfDNA)起到肿瘤指纹的作用，可以检测到标志着疾病变异和进展的基因变化。作为一种临床工具，它可能会取代 目前可用的、相对不敏感的脑肿瘤诊断方法。作为一种科学工具，在脑脊液中发现新的肿瘤cfDNA突变将使人们能够更深入地了解肿瘤生物学，并更忠实地建立这些疾病的动物模型。具体目标1：开发新型微流控芯片，分离和鉴定原发和转移性脑肿瘤患者脑脊液中的cfDNA。具体目标2：改进新的测序技术以表征中枢神经系统肿瘤患者脑脊液中的肿瘤cfDNA。探讨肿瘤cfDNA测序取代细胞学诊断软脑膜转移瘤的可行性。具体目的3：通过建立脑脊液中cfDNA的单基因拷贝数变异测序方法，对原发脑肿瘤进行亚型分析。摘要：脑肿瘤脑脊液中的cfDNA在追踪癌症的突变特征、诊断疾病和指导治疗方面显示出巨大的希望。在这里加速的技术可能会彻底改变对软脑膜转移的认识，并加深我们对脑瘤进展的科学理解。

 DESCRIPTION (provided by applicant): We are developing an innovative, minimally invasive method to study the genetic spectrum of tumors metastatic and primary to the central nervous system (CNS). Cell free DNA (cfDNA) acts as a tumor fingerprint, allowing detection of genetic alterations that mark the variation and progression of disease. As a clinical tool, it may supplant the currently available and relatively insensitive methods of brain tumor diagnosis. As a scientific tool, novel tumor cfDNA mutations identified in CSF will allow for great insight into tumor biology, and more faithful animal modeling of these diseases. Specific Aim 1: Develop novel microfluidic chips to isolate and characterize cfDNA within the CSF of patients with primary and metastatic brain tumors. Specific Aim 2: Refine new sequencing techniques to characterize tumor cfDNA in CSF from patients with CNS tumors. Determine the feasibility of supplanting cytology with tumor cfDNA sequencing in the diagnosis of leptomeningeal metastasis. Specific Aim 3: Subtype primary brain tumors through the development of single-gene copy number variation sequencing of cfDNA in CSF. Summary: cfDNA in CSF from brain tumors shows great promise to track cancer's mutation profile, diagnose disease, and inform treatment. The techniques accelerated here may revolutionize the recognition of leptomeningeal metastases, and deepen our scientific understanding of brain tumor progression.