Molecular Diagnosis and Prognosis in Aggressive Lymphoma

描述（由申请人提供）：本申请是根据 PAR-10-126，《癌症特征评估战略合作伙伴关系》[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分析用于区分 5 种最常见侵袭性 B 细胞非霍奇金淋巴瘤的预后基因特征测定将被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)、基因表达的直接多重测量 (Nanostring) 和定量核酸酶保护测定（高通量基因组学）。所有 3 个平台将在由 SAIC-Frederick 运营的 NCI-Frederick 患者特征中心 (PCC) 和第二个学术研究中心同时进行比较。在第二阶段，“获胜”的平台将在 PCC 和另外 2 个中心进行测试。在第二阶段，测试的基因将被扩展以包括预后特征。与我们之前使用快速冷冻组织进行的发现工作不同。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，以实现最广泛的临床应用。LLMPP 凭借进行“黄金标准”GEP 实验来完成这项工作，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。将侵袭性淋巴瘤分子诊断的先前进展转化为新的临床范例，以实现准确的诊断、预后和治疗靶点识别。

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.