Validation of Prognostic and Diagnostic molecular tests in Mesothelioma

描述（申请人提供）：恶性胸膜间皮瘤（MPM）是一种高度致命的癌症，缺乏有效的治疗方法。即使是治疗这种恶性肿瘤的基本要素，如权宜的诊断和准确的预后仍然具有挑战性，需要积极的手术切除以确定分期和预后。我们之前已经描述了一种使用基因表达比将全基因组表达研究转化为临床相关测试的新技术，可以准确预测许多临床参数，如癌症的诊断和预后。具体来说，我们开发了一种测试来区分MPM和肺癌，以及另一种测试来预测MPM患者接受手术的结果。这些基于比率的测试需要少量的肿瘤RNA，以统计显着的方式预测MPM手术患者的诊断和临床结果。我们建议通过识别额外的基因来扩大这些测试的诊断能力，以便在怀疑MPM时做出正确的诊断。这种方法可以作为基因组的模板。鉴别诊断算法是病理学的辅助手段。然后，我们将在其他标本上改进和验证这些测试。我们还建议改进和发展方法，以便微创或使用图像引导的细针抽吸获得的标本可以进行适当的测试。为了将预后和诊断测试带到床边，它们需要与实际的患者管理相关，标准化和验证，最好在多中心环境中进行。我们建议在我们机构的临床试验和多中心研究中招募更多的患者，通过细针穿刺和微创活检前瞻性地验证预后测试。这项提议的工作将利用可以测量整个肿瘤基因组表达（RNA）的新技术来开发可以轻松应用于患者的新测试。除了提供将改变MPM患者管理的新测试——通过最终使诊断手术不必要，并使某些患者免于不必要的大手术——这项工作将使我们能够开发一个诊断、预后和治疗指导平台，最终可用于其他癌症和人类疾病，从而允许对癌症和其他疾病进行个体基因组指导治疗。

DESCRIPTION (provided by applicant): Malignant pleural mesothelioma (MPM) is a highly lethal cancer for which effective therapy is lacking. Even the basic elements to treatment for this malignancy such as expedient diagnosis and accurate prognosis remain challenging and aggressive surgical extirpation is required for definitive staging and prognosis. We have previously described a novel technique using gene expression ratios to translate whole genome expression studies into clinically relevant tests that can accurately predict many clinical parameters such as diagnosis and prognosis in cancers. Specifically, we developed a test to distinguish between MPM and lung cancer and another test to predict outcome in MPM patients undergoing surgery. These ratio-based tests require small amounts of tumor RNA, to predict in a statistically significant manner diagnosis as well as clinical outcome for patients undergoing surgery for MPM. We propose to expand the diagnostic capability of these tests by identifying additional genes to make the correct diagnosis whenever MPM is suspected. This methodology can serve as a template for a genomic. Differential diagnosis algorithm to be an adjunct for pathology. We will then refine and validate these tests on additional specimens. We also propose to refine and develop the methodology so that specimens obtained minimally invasively or while using image-guided fine needle aspiration can be appropriately tested. To bring the prognostic and diagnostic tests to bedside they need to be made relevant to actual patient management, be standardized and be validated, preferably in a multi-center setting. We propose to prospectively validate the prognostic tests both with fine needle aspiration and minimally invasive biopsies in additional patients enrolled prospectively in clinical trials at our institution and in a multi center study. The proposed work will capitalize on new technology that can measure the expression (RNA) of the entire tumor genome to develop new tests that can be easily applied to patients. In addition to providing new tests that will alter the management of MPM patients--by eventually making surgery for diagnosis unnecessary and save certain patients from unnecessary major surgery-- this work will allow us to develop a diagnostic, prognostic and treatment directing platform that can be ultimately used for other cancers and human diseases to allow individual genome directed therapy for cancer and other diseases.