Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluid

项目摘要 目前没有生物标志物用于高级别胶质瘤的管理。 因此，患者通常需要进行侵入性活检或手术切除， 区分疾病进展与治疗相关变化，量化疾病负担， 追踪这些难以治疗的癌症的分子进化。在迄今为止的工作中，我们 已经能够证明CSF是肿瘤衍生DNA的丰富储存库。我们现在 在该工作的基础上扩展开发一种多分析物测定， 变化、亚染色体变化和体细胞突变。我们通过观察 多个分析物，我们将能够提高测定的灵敏度， 对癌症基因型有更全面的了解。该多分析物检测试剂盒的特异性 将使用来自非癌症个体的CSF进行测试。在短期内，我们预计， 这种方法将使我们能够生成能够跟踪脑癌的个性化生物标志物， 提供对肿瘤基因型的深入了解，从而使临床医生能够更明智地 实时决策。从长远来看，我们预计，我们可以获得更广泛的了解， 在非肿瘤状态下，如多发性硬化症、神经结节病 或者感染这可能会对我们诊断和监测其他疾病的能力产生广泛的影响。 影响大脑的疾病

PROJECT SUMMARY There are no biomarkers that are currently used in the management of high-grade gliomas. Therefore, patients are often required to undergo invasive biopsies or surgical resection to differentiate disease progression from treatment related changes, quantify disease burden and track the molecular evolution of these difficult to treat cancers. In work performed to date, we have been able to demonstrate that CSF is a rich reservoir for tumor derived DNA. We are now expanding upon that work to develop a multi-analyte assay that will incorporate copy number changes, sub-chromosomal changes and somatic mutations. We anticipate that by looking at multiple analytes we will be able to improve sensitivity of the assay while also being able to have a more wholistic understanding of the cancer genotype. The specificity of this multi-analyte assay will be tested using CSF from individuals without cancer. In the short term, we anticipate that this approach will allow us to generate personalized biomarkers capable of tracking brain cancers and providing insights into the tumor genotype, thereby allowing clinicians to make more informed decisions in real-time. In the long term, we anticipate that we can gain a broader understanding of the CSF DNA composition in non-neoplastic states, such as multiple sclerosis, neurosarcoidosis or infection. This could have broad ranging impact on our ability to diagnose and monitor other disorders impacting the brain.