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

 描述（由申请人提供）：我们正在开发一种创新的微创方法来研究转移性和原发性中枢神经系统（CNS）肿瘤的遗传谱。无细胞DNA（cfDNA）作为肿瘤指纹，允许检测标记疾病变化和进展的遗传改变。作为一种临床工具，它可能会取代 目前可用且相对不敏感的脑肿瘤诊断方法。作为一种科学工具，在CSF中鉴定出的新型肿瘤cfDNA突变将使人们能够深入了解肿瘤生物学，并对这些疾病进行更忠实的动物建模。具体目标1：开发新型微流控芯片，以分离和表征原发性和转移性脑肿瘤患者CSF中的cfDNA。具体目标2：完善新的测序技术，以表征CNS肿瘤患者CSF中的肿瘤cfDNA。确定在诊断软脑膜转移中用肿瘤cfDNA测序取代细胞学检查的可行性。具体目标3：通过开发CSF中cfDNA的单基因拷贝数变异测序对原发性脑肿瘤进行亚型分析。来自脑肿瘤的CSF中的cfDNA显示出跟踪癌症突变谱、诊断疾病和告知治疗的巨大希望。这里加速的技术可能会彻底改变对软脑膜转移的认识，并加深我们对脑肿瘤进展的科学理解。

 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.