Molecular Diagnosis of Sarcomas

描述(由申请人提供)： 我们将详细阐述血清定量聚合酶链式反应(QPCR)和外周血RT-QPCR 用于诊断肉瘤存在的测试。我们的目标是构建简单的血液 筛查肉瘤高危人群的测试，以评估最初的 肿瘤，以评估肉瘤患者的治疗和/或跟踪 曾因肉瘤接受过治疗。最初选择肉瘤是因为我们发现 血清中有相当数量的肿瘤细胞DNA裂解。这使我们能够 提出一种基于抑癌基因数量差异的通用检验方法 肉瘤中的癌基因。随后，更具体的测试变成了 可能与胃肠道间质瘤和胃肠道间质瘤中c-kit基因的异常有关 具有明确肉瘤类型特征的特定易位。我们添加这些 对我们之前的应用程序进行了更具体的测试，该应用程序基于 仅限测试。 1.检测原发肉瘤的QPCR标志物 改变和显示特定易位的RT-QPCR标记。 2.同时监测血清，以确定其中的QPCR异常 和/或外周血以筛选特异性RT-QPCR标记物 易位。这些决定的有用性得到了我们的 初步结果显示存在QPCR血清异常 未经治疗的肉瘤患者。 3.纵向监测血清和外周血液以筛查这些 分子异常和(如有必要)用于检测转移的新异常 和/或临床上可能不明显的复发。 如果我们检测到有用的血清QPCR异常和/或外周血异常 在第一阶段的个别情况下，我们会把第二阶段的研究扩展至 进行在特定情况下有用的纵向定量聚合酶链式反应分析。我们将使用 对高危人群和接受治疗的人群进行诊断的测试，以监测 在治疗前和治疗期间进行癌细胞裂解，以监测其疗效 癌症治疗和检测复发。这是作为R21(一)提出的 年)/R33(三年期)补助金，以确定这些研究的可行性 肉瘤发生在R21期。如果需要更多的研究，R33阶段将 支持所需的较长期纵向研究，以证明 用这项测试来跟踪肉瘤的进程。

DESCRIPTION (provided by applicant): We will elaborate serum quantitative-PCR (QPCR) and peripheral blood RT-QPCR tests to diagnose the presence of sarcomas. We aim to construct simple blood tests to screen people at increased risk for sarcoma, to evaluate the initial tumor, to assess therapy of patients with sarcoma and/or to follow people who have been treated for sarcoma. Sarcomas were chosen initially because we found appreciable amounts of lysed tumor cell DNA in the serum. This enabled us to propose a generic test based on quantitative differences of tumor suppressors and oncogenes in sarcoma. Subsequently, more specific tests have become available involving aberration of the c-kit gene in GI stromal tumors and specific translocations that characterize defined sarcoma types. We add these more specific tests to our previous application that was based on the generic tests only. 1. Test the primary sarcoma to assay the QPCR markers that show quantitative changes and the RT-QPCR markers that show specific translocations. 2. Monitor the serum simultaneously to determine the QPCR anomalies therein and/or the peripheral blood to screen for specific RT-QPCR markers of translocation. The usefulness of these determinations is supported by our preliminary results demonstrating the presence of QPCR serum anomalies in untreated sarcoma patients. 3. Monitor the serum and peripheral blood longitudinally to screen for these molecular anomalies and (if necessary) new anomalies to detect metastases and/or recurrence that might not be apparent clinically. If we detect useful serum QPCR anomalies and/or peripheral blood anomalies in particular situations in phase I, we will expand the studies in phase II to perform longitudinal QPCR assays useful in a given situation. We will use the test to perform diagnosis of at-risk and treated populations, to monitor cancer cell lysis before and during treatment, to monitor the efficacy of cancer treatments and to detect recurrences. This is proposed as an R21 (one year)/R33 (three year) grant to determine the feasibility of these studies for sarcomas in the R21 phase. If more studies are indicated, the R33 phase would support the longer-term longitudinal studies required to demonstrate how best to use this test to follow the course of sarcomas.