exRNA Biomarkers for Human Glioma

描述(由申请人提供)： 人脑胶质瘤的非侵入性诊断可以改善这种疾病患者的生活质量，因为它允许患者得到直接诊断或分层治疗，而不需要侵入性脑活检。在这项研究中，研究人员提议开发新的细胞外RNA生物标志物来诊断人脑胶质瘤肿瘤。使用肿瘤特异性细胞外RNA(ExRNA)基因变化的优先小组，我们将测试不同的竞争技术(qPCR、数字PCR、外显子组测序和DMR)，以检测脑胶质瘤患者血液和脑脊液中的exRNA候选生物标记物。在UH3研究阶段，我们将建立一个机构联盟，提供快速预期的肿瘤组织脑脊液和脑胶质瘤患者血液的收集，并建立脑脊液和血液采集的通用方案，以支持临床诊断脑胶质瘤的exRNA分析。然后，我们将使用血液或脑脊液exRNA分析(从UH2期开始优先)，并在两个临床患者群体中进行检测，以验证exRNA对胶质瘤的诊断：1)疑似低级别胶质瘤，2)疑似高级别胶质瘤。将测试的典型标记物将包括在低级别肿瘤中检测IDH1突变，在高级别肿瘤中检测EGFRvIII。我们期待着能够确定脑脊液或血液检测用于诊断人脑胶质瘤的敏感性和特异性。我们还预计，在难以活检的肿瘤患者中，这项研究的结果将产生一种非侵入性诊断脑肿瘤的方法，从而减少对侵入性脑手术的需求，并适当地对患者进行靶向治疗。

DESCRIPTION (provided by applicant): The non-invasive diagnosis of human glioma could improve the quality of life of patients with this disease by allowing patients to be directly diagnosed or stratified for treatment without the need of an invasive brain biopsy. In this study, the investigators propose to develop novel extracellular RNA biomarkers for the diagnosis of human glioma tumors. Using a prioritized panel of tumor specific extracellular RNA (exRNA) genetic changes, we will test different competing technologies (qPCR, digital PCR, exome sequencing, and DMR) for detecting exRNA candidate biomarkers in blood and CSF of glioma patients. In the UH3 phase of study, we will create a consortium of institutions to provide rapid prospective collection of tumor tissue CSF, and blood from glioma patients and establish common protocols for CSF and blood collection to support clinical diagnostic glioma exRNA assays. We will then validate the diagnosis of glioma by exRNA using blood or CSF exRNA assays (as prioritized from the UH2 phase) and tested in two clinical patient population; 1) suspected low grade and 2) suspected high grade glioma. Prototypical markers that will be tested will include the detection of IDH1 mutations in low grade tumors and EGFRvIII in high grade tumors. We anticipate the ability to determine the sensitivity and specificity with which a CSF or blood test can be used to diagnosis human glioma. We further anticipate that in patients with difficult to biopsy tumors, the results o this study will yield a method for diagnosing brain tumors non-invasively thus reducing the need for invasive brain surgery and appropriately stratifying patients for targeted therapies.