Molecular Diagnosis of Sarcomas

描述（由申请人提供）： 我们将详细阐述血清定量PCR（QPCR）和外周血RT-QPCR 检查以诊断肉瘤的存在。我们的目标是构建简单的血液 筛查肉瘤风险增加的人的测试，以评估最初的 肿瘤，以评估肉瘤患者的治疗和/或跟踪那些 都曾接受过肉瘤治疗最初选择肉瘤是因为我们发现 在血清中存在可观量的裂解的肿瘤细胞DNA。这使我们能够 提出一种基于肿瘤抑制因子数量差异的通用测试 和癌基因。随后，更具体的测试已成为 涉及胃肠道间质瘤中c-kit基因的畸变， 特定类型肉瘤的特征性易位。我们加上这些 对我们以前的应用程序进行更具体的测试， 仅测试。 1.检测原发性肉瘤，以测定QPCR标记物， 变化和显示特定易位的RT-QPCR标记。 2.同时监测血清以确定其中的QPCR异常 和/或外周血来筛选特异性RT-QPCR标记物， 易位这些测定的有用性得到了我们的支持。 初步结果表明， 未经治疗的肉瘤患者。 3.纵向监测血清和外周血以筛查这些 分子异常和（如有必要）新的异常以检测转移 和/或复发，可能在临床上不明显。 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，我们将扩大第二阶段的研究， 进行在给定情况下有用的纵向QPCR测定。我们将使用 对高危人群和接受治疗人群进行诊断的检测， 治疗前和治疗期间的癌细胞裂解，以监测 癌症治疗和检测复发。这是作为R21（一个 R33（三年）赠款，以确定这些研究的可行性， R21期肉瘤如果需要更多的研究，R33阶段将 支持所需的长期纵向研究，以证明如何最好地 用这个测试来追踪肉瘤的发展过程。

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.