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。即使是早期诊断和准确预后等治疗的基本要素仍然具有挑战性，需要积极的手术切除才能确定分期和预后。我们之前已经描述了一种新的技术，使用基因表达比率将全基因组表达研究转化为临床相关测试，可以准确预测许多临床参数，如癌症的诊断和预后。具体地说，我们开发了一种用于区分MPM和肺癌的测试，以及另一种用于预测接受手术的MPM患者结果的测试。这些基于比率的测试需要少量的肿瘤RNA，以统计意义上的方式预测MPM手术患者的诊断和临床结果。我们建议通过识别更多的基因来扩展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分析的模板。鉴别诊断算法作为病理学的辅助手段。然后，我们将在更多的样本上改进和验证这些测试。我们还建议改进和发展方法学，以便通过最小限度的侵入性或在使用图像引导的细针抽吸时获得的标本可以进行适当的测试。为了将预测和诊断测试带到床边，需要使它们与实际的患者管理相关，标准化并进行验证，最好是在多中心设置中。我们建议在我们机构和一项多中心研究中，前瞻性地通过细针抽吸和微创活组织检查对更多参加临床试验的患者的预后检测进行验证。这项拟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变得不必要并将某些患者从不必要的大手术中拯救出来--这项工作还将使我们能够开发一个最终可用于其他癌症和人类疾病的诊断、预后和治疗指导平台，从而允许对癌症和其他疾病进行个人基因组定向治疗。

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.