Molecular Diagnosis and Prognosis in Aggressive Lymphoma

侵袭性淋巴瘤的分子诊断和预后

• 批准号: 8686600
• 负责人: Lisa Rimsza
• 金额: $ 56.59万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8686600
• 关键词: Address; Algorithms; Amendment; B-Cell Lymphomas; B-Cell NonHodgkins Lymphoma; Biological Assay; Biopsy; Clinical; Clinical Trials; Data; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Formalin; Freezing; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Genomics; Gold; Human; Laboratories; Lymphoma; Malignant Neoplasms; Measurement; Methods; Molecular Diagnosis; Molecular Profiling; Nuclease Protection Assays; Oligonucleotide Microarrays; Paraffin Embedding; Patient Care; Patients; Performance; Phase; Principal Investigator; Research; Site; Technology; Testing; Tissues; Translating; United States; United States Centers for Medicare and Medicaid Services; United States Food and Drug Administration; Work; Writing; base; clinical application; density; design; leukemia/lymphoma; nano-string; outcome forecast; performance tests; prognostic; research study; response; therapeutic target

DESCRIPTION (provided by applicant): This application is written in response to PAR-10-126, Strategic Partnering to Evaluate of Cancer Signatures [SPECS II] (U01)." The proposed project focuses on translating our previously discovery-oriented gene expression signatures into laboratory tests for lymphoma clinical trials and patient care. Our research consortium, the Lymphoma and Leukemia Molecular Profiling Project (LLMPP) will design and validate a multi-analyte diagnostic and prognostic gene signature assay to differentiate the 5 most common aggressive B cell non-Hodgkin lymphomas. Each lymphoma subtype will then be further classified into prognostic groups. Three methods of gene expression profiling with demonstrated utility in our feasibility testing will be rigorously evaluated including high density oligonucleotide arrays (Affymetrix), direct multiplexed measurement of gene expression (Nanostring), and quantitative nuclease protection assay (High Throughput Genomics). In Phase 1 diagnostic genes will be tested at all 3 platforms will be compared simultaneously at the Patient Characterization Center (PCC) at NCI-Frederick, operated by SAIC-Frederick and a second academic study site. In Phase 2, the "winning" platform will be tested at the PCC and 2 additional sites. In Phase 2, tested genes will be expanded to include prognostic signatures. Data will be generated in such a way as to be appropriate for submission for regulatory review. As opposed to our previous discovery work that was performed with snap frozen tissues which are scare and only available at academic centers, this project will use formalin fixed, paraffin embedded tissues (FFPET), which are routinely available from all biopsies, in order to have the broadest clinical application. The LLMPP is uniquely posed to accomplish this work by virtue of having performed the "gold standard" GEP experiments that define the diagnostic and prognostic distinctions in these lymphomas as well as holding matching FFPET blocks from the same cases. Hence, this proposed research addresses a critical unmet need to translate previous advances in the molecular diagnosis of aggressive lymphomas into a new clinical paradigm for accurate diagnosis, prognosis, and therapeutic target identification.

描述（由申请人提供）：本申请是根据 PAR-10-126，评估癌症特征的战略合作 [SPECS II] (U01) 编写的。”拟议项目的重点是将我们以前以发现为导向的基因表达特征转化为淋巴瘤临床试验和患者护理的实验室测试。我们的研究联盟，淋巴瘤和白血病分子谱分析项目 (LLMPP) 将设计和 验证多分析物诊断和预后基因特征测定，以区分 5 种最常见的侵袭性 B 细胞非霍奇金淋巴瘤。然后，每种淋巴瘤亚型将进一步分为预后组。将严格评估在我们的可行性测试中已证明有用的三种基因表达谱分析方法，包括高密度寡核苷酸阵列（Affymetrix）、直接多重分析 基因表达测量（纳米线）和定量核酸酶保护测定（高通量基因组学）。在第一阶段，诊断基因将在所有 3 个平台上进行测试，并在 NCI-Frederick 的患者特征中心 (PCC)（由 SAIC-Frederick 运营）和第二个学术研究中心同时进行比较。在第二阶段，“获胜”平台将在 PCC 和另外 2 个站点进行测试。在 第二阶段，测试的基因将扩大到包括预后特征。数据将以适合提交监管审查的方式生成。与我们之前使用快速冷冻组织进行的发现工作相反，这种组织很稀缺且仅在学术中心提供，该项目将使用福尔马林固定的石蜡包埋组织 (FFPET)，这些组织通常可从所有活检中获得，以便 最广泛的临床应用。 LLMPP 具有独特的优势来完成这项工作，因为它进行了“黄金标准”GEP 实验，这些实验定义了这些淋巴瘤的诊断和预后区别，并持有来自同一病例的匹配 FFPET 块。因此，这项拟议的研究解决了一个未满足的关键需求，即将侵袭性淋巴瘤分子诊断的先前进展转化为新的临床方法 准确诊断、预后和治疗靶标识别的范例。