Molecular and clinical evaluation of the glioma patient experience to anticipate modern outcomes and guide patient care

对神经胶质瘤患者经历进行分子和临床评估，以预测现代结果并指导患者护理

基本信息

批准号：
10226954
负责人：
Laila M Poisson
金额：
$ 34.65万
依托单位：
HENRY FORD HEALTH SYSTEM
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：
2018-08-08 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10226954
关键词：
19q Accounting Address Adjuvant Affect Astrocytes Biological Assay Brain Brain Neoplasms Caring Cells Chromosome Deletion Clinical Clinical Informatics Copy Number Polymorphism DNA DNA Methylation DNA Sequence Data Databases Diagnosis Diagnostic Dideoxy Chain Termination DNA Sequencing Disease Disease Progression Documentation Freezing Future Genes Genomics Glioma Goals Guidelines Health system Histologic Histology Histopathologic Grade Hospitals Isocitrate Dehydrogenase Longterm Follow-up Malignant Neoplasms Methylation Microscope Modeling Modernization Molecular Molecular Diagnosis Molecular Profiling Mutation Neuroglia Oligodendroglia Outcome Paper Patient Care Patient-Focused Outcomes Patients Pattern Phenotype Precision therapeutics Prediction of Response to Therapy Prior Therapy Prognosis Progression-Free Survivals Progressive Disease Prospective Studies Publishing Radiation therapy Records Recurrent disease Regimen Research Research Personnel Resources Retrospective Studies Sampling Scheme Specimen Statistical Models Survivors Testing The Cancer Genome Atlas Therapeutic Time Tissues Translating Tumor Bank Update Variant Work World Health Organization arm base cell type clinical decision support clinical practice data resource design epigenomics exome sequencing expectation experience genomic profiles improved insight methylome molecular diagnostics molecular marker novel patient response personalized diagnostics precision medicine prognostic promoter public repository research clinical testing response risk stratification standard care temozolomide therapy outcome treatment response treatment strategy tumor tumor DNA

项目摘要

Project Summary Landmark papers published recently by us, and others, mark the new era of molecular diagnoses and precision therapy for glioma. In the summer of 2016, the World Health Organization (WHO) published updated diagnosis criteria for glioma that include molecular markers, taking a first step toward a molecularly precise diagnosis. It is our long-term goal to capitalize on the longitudinal resources of brain tumor banks to rapidly assess molecular hypotheses for prognosis and treatment of glioma. With the significant contribution of 240 cases from Henry Ford Hospital (HFH), an effort to molecularly and clinically profile glioma was started by The Cancer Genome Atlas (TCGA) project. Capitalizing on our clinically annotated brain tumor bank at HFH, we will focus on therapeutic outcomes, recurrent disease, and extended survival, which were not captured in the TCGA project. For this work, we have constructed an interdisciplinary team of collaborators, with clinical and informatics expertise, to profile an additional 340 glioma cases (WHO grade II-IV). In total, we will assess 700 tumor specimens (FFPE/frozen) from the HFH tumor bank (2001-present), representing both primary and matched progressive disease (Aim 1). Molecular data will be generated by exome sequencing to assess DNA sequence and copy number variants, targeted Sanger sequencing to profile the TERT promoter, and DNA methylation array assays to profile the methylome. Clinical annotation from our tumor bank, including long-term follow-up and therapy regimens, will be added to each of the 550 profiled glioma cases. The resulting comprehensively-annotated tumor bank will be an invaluable resource for queries of clinical-molecular associations and the progression of disease, made available to researchers at HFH and beyond. In this proposal we use our database to address two analytical aims: (Aim 2) to carefully design statistical models of prognosis and therapy response among modern diagnosis classes using retrospective records; (Aim 3) to identify genomic differences, per patient, arising over the course of treatment and progression, which we expect will impact therapy decisions and inform standard treatments strategies. As part of the third aim, we will also explore the genomic patterns and clinical response of patients with exceptional survival, which may indicate differential molecular diagnosis or suggest therapeutic avenues for extending survival in others.

项目概要我们和其他人最近发表的具有里程碑意义的论文标志着分子诊断和精确度的新时代神经胶质瘤的治疗。 2016年夏天，世界卫生组织（WHO）发布了最新诊断结果神经胶质瘤的标准包括分子标记，迈出了分子精确诊断的第一步。这是我们的长期目标是利用脑肿瘤库的纵向资源来快速评估分子水平神经胶质瘤的预后和治疗的假设。亨利·福特240个案例的重大贡献 Hospital (HFH)，癌症基因组图谱发起了一项对神经胶质瘤进行分子和临床分析的工作（TCGA）项目。利用 HFH 的临床注释脑肿瘤库，我们将专注于治疗 TCGA 项目中未涵盖的结果、复发性疾病和延长生存期。对于这项工作，我们建立了一个跨学科的合作团队，具有临床和信息学专业知识，以分析另外 340 例神经胶质瘤病例（WHO II-IV 级）。我们总共将评估 700 个肿瘤标本（FFPE/冷冻）来自 HFH 肿瘤库（2001 年至今），代表原发性疾病和相匹配的进展性疾病（目标 1）。分子数据将通过外显子组测序生成，以评估 DNA 序列和拷贝数变异，靶向桑格测序以分析 TERT 启动子，并通过 DNA 甲基化阵列分析来分析甲基化组。我们的肿瘤库的临床注释，包括长期随访和治疗方案，将添加到 550 个神经胶质瘤病例中的每一个中。由此产生的全面注释的肿瘤库将是提供了用于查询临床分子关联和疾病进展的宝贵资源 HFH 及其他机构的研究人员。在本提案中，我们使用我们的数据库来解决两个分析目标：（目标 2）仔细设计现代诊断类别中的预后和治疗反应的统计模型使用回顾记录；（目标 3）识别每个患者在治疗过程中出现的基因组差异治疗和进展，我们预计这将影响治疗决策并为标准治疗提供信息策略。作为第三个目标的一部分，我们还将探索患者的基因组模式和临床反应具有出色的生存率，这可能表明差异分子诊断或建议治疗途径延长他人的生存期。