Molecular Diagnosis, Prognosis, and Therapeutic Targets in Lymphoma

淋巴瘤的分子诊断、预后和治疗靶点

基本信息

批准号：
9788307
负责人：
Lisa Rimsza
金额：
$ 200.68万
依托单位：
MAYO CLINIC ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-19 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9788307
关键词：
Adult B-Cell Lymphomas B-Lymphocytes BCL2 gene Bioinformatics Biological Biology Biometry Biopsy Categories Cessation of life Child Classification Clinical Clinical Research Communication Copy Number Polymorphism DNA Sequence Alteration Data Data Analyses Diagnosis Diagnostic Diagnostic Procedure Diffuse Disease Ensure Epigenetic Process Experimental Designs Gene Expression Gene Expression Profile Genetic Genomics Goals Grant Immunophenotyping Incidence Individual Intention International Ki-1 Large-Cell Lymphoma Knowledge Leadership Legal patent Lymphoma Malignant Neoplasms Malignant lymphoid neoplasm Mantle Cell Lymphoma Medical Oncologist Messenger RNA Methods Molecular Molecular Biology Molecular Diagnosis Molecular Profiling Monitor Mutation Outcome Output Pathologic Pathologist Pathology Pathway interactions Patient Care Patients Peripheral Phenotype Pre-Clinical Model Prevalence Publications Rare Diseases Recording of previous events Refractory Disease Relapse Research Research Design Sampling Scientist Signal Pathway Site Specific qualifier value Supervision System T-Cell Lymphoma Technical Expertise Technology Therapeutic Tissues Translational Research Transplantation Treatment Failure Tumor-Derived United States Work accurate diagnosis assay development base bench to bedside cancer diagnosis cancer subtypes clinical translation commune companion diagnostics diagnosis quality diagnostic assay functional genomics improved large cell Diffuse non-Hodgkin&apos s lymphoma leukemia/lymphoma molecular subtypes new therapeutic target novel diagnostics off-patent outcome forecast phase 3 testing predictive test prognostic prognostic tool programs repository survival prediction technique development therapeutic target transcriptome tumor tumor xenograft

项目摘要

This application is submitted on behalf of the Lymphoma and Leukemia Molecular Profiling Project (LLMPP), a long-standing, tightly integrated, international research consortium based in the United States with a highly successful track-record of discovery and clinical translation profoundly impacting the known biology, classification, and treatment of lymphoma. In the current application, we propose 4 complimentary projects to extend our understanding of difficult to treat lymphomas including (1) Aggressive B cell lymphomas (Dr. Scott), (2) Mantle cell lymphoma (Dr. Campo), (3) Peripheral T cell lymphoma (Dr. Iqbal), and (4) Anaplastic large cell lymphoma (Dr. Feldman). The overall research strategy will extend our gene expression characterization and initial sequencing studies into larger more comprehensive analyses of genomics (including sequence, rearrangements, copy number variations, and epigenetics) in order to identify new diagnostic categories with unique biological features, prognoses, and therapeutic targets. In Aggressive B cell lymphomas there is a pressing need to understand the appropriate diagnostic categorization as related to treatment failure. Mantle cell lymphoma has an extremely variable range of outcomes from slow growing tumors requiring minimal therapy to those requiring transplant and thus likely represents more than one disease. Peripheral T cell lymphoma-Not otherwise specified is a nearly orphan disease with few patients surviving despite intense therapy. Anaplastic large cell lymphoma is a rare disease with variable outcome and different genetics in adults versus children. The Projects' details are described in additional abstracts. We overall hypothesize that aggressive B and T cell lymphomas can be further subdivided by genomic alterations including translocation partners, breakpoints, mutations, copy number alterations, epigenetics, and phenotype and that these features can be functionally characterized and used to improve patient care. As in our prior work, the bedrock of these translational projects will be sophisticated analyses of primary tissue biopsies from patients that are communally reviewed by a panel of pathologists for accurate diagnosis, quality, and tumor content. The individual scientific projects of this grant will synergize by sharing tissues, scientific strategies, data, analysis techniques, and assay development expertise. This teamwork will be complimented by functional genomics and patient derived tumor xenograft systems for pre- clinical modeling. The Projects will work closely with biostatistics for study design and analysis and use bioinformatics to analyze high throughput data. Thus, the proposed cores include Administrative (Dr. Rimsza), Pathology (Dr. Cook), Functional Genomics (Dr. Staudt), Preclinical Models and Therapeutics (Dr. Inghirami) and Biostatistics & Bioinformatics (Dr. Wright). The overall intention is to use genomic studies as a platform to better understand disease biology, develop more correct classification and prognosis, and identify and characterize therapeutic targets; with a long-term goal of enhancing patient survival.

该申请代表淋巴瘤和白血病分子分析项目（LLMPP）提交在美国长期存在，紧密整合的国际研究财团，高度高度发现和临床翻译的成功曲目记录深远影响已知生物学，分类和治疗淋巴瘤。在当前申请中，我们提出了4个免费项目为了扩展我们对难以治疗淋巴瘤的理解，包括（1）攻击性B细胞淋巴瘤（博士 Scott），（2）地幔细胞淋巴瘤（Campo博士），（3）外周T细胞淋巴瘤（IQBAL博士）和（4）大细胞淋巴瘤（Feldman博士）。总体研究策略将扩展我们的基因表达对更大的基因组分析进行表征和初步测序研究（包括序列，重排，拷贝数变化和表观遗传学），以识别新的具有独特的生物学特征，预后和治疗靶标的诊断类别。在激进的B细胞中淋巴瘤迫切需要了解与治疗失败。地幔细胞淋巴瘤的结局范围很大，生长缓慢需要对需要移植的患者进行最少治疗的肿瘤，因此可能代表多个疾病。周围T细胞淋巴瘤不是另外指定的是几乎孤儿疾病，患者很少尽管治疗强烈，但仍在生存。那型大细胞淋巴瘤是一种罕见疾病，有变化的结果和成人与儿童的不同遗传学。项目的详细信息在其他摘要中描述。我们总体上假设攻击性B和T细胞淋巴瘤可以通过基因组进一步细分更改，包括易位合作伙伴，断点，突变，拷贝数更改，表观遗传学和表型，这些特征可以在功能上表征和用于改善患者护理。就像我们先前的工作一样，这些翻译项目的基石将是复杂的病理学家小组对患者的原发组织活检进行分析准确的诊断，质量和肿瘤含量。这笔赠款的个别科学项目将协同作用共享组织，科学策略，数据，分析技术和测定开发专业知识。这团队合作将由功能基因组学和患者衍生的肿瘤异种移植系统的称赞临床建模。这些项目将与生物统计学紧密合作，用于研究设计和分析和使用生物信息学以分析高吞吐量数据。因此，拟议的核心包括行政（博士 Rimsza），病理学（库克博士），功能基因组学（Staudt博士），临床前模型和治疗学（博士 Inghirami）和生物统计学和生物信息学（Wright博士）。总体意图是将基因组研究用作更好地了解疾病生物学，发展更正确的分类和预后的平台，并确定并表征治疗靶标；具有增强患者生存的长期目标。