Exome-wide screening for common mutations in lymphoma

淋巴瘤常见突变的全外显子组筛查

基本信息

批准号：
8279186
负责人：
Sandeep Dave
金额：
$ 16.85万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-10 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8279186
关键词：
1-Phosphatidylinositol 3-Kinase Accounting Address Alleles Biology Cell Cycle Cessation of life Chemotherapy-Oncologic Procedure Clinical DNA DNA Sequence Development Diagnosis Dideoxy Chain Termination DNA Sequencing Disease Employee Strikes Exhibits Exons Frequencies Gene Expression Gene Expression Profiling Genes Genetic Genetic Variation Genome Goals Heterogeneity Institution Lymphoma Malignant Neoplasms MicroRNAs Molecular Molecular Profiling Mutation Non-Hodgkin&apos s Lymphoma Oncogenic Pathogenesis Pathway interactions Patients Process Proteins Reagent Recurrence Regimen Relapse Relative (related person)Research Role Screening procedure Signal Transduction Solutions Subgroup Validation Variant Work base chemotherapy clinically relevant cost early experience exome genetic variant genome sequencing high throughput technology improved insight large cell Diffuse non-Hodgkin&apos s lymphoma molecular phenotype novel therapeutics outcome forecast protein expression response therapeutic target tumor

项目摘要

DESCRIPTION (provided by applicant): Diffuse large B cell lymphoma (DLBCL) is the most common form of lymphoma and accounts for nearly 40% of all cases of non Hodgkin lymphoma. The disease exhibits a striking clinical heterogeneity. Less than half of the patients are cured with standard multi-agent chemotherapy. On the other hand, over half the patients experience early progression, relapse and death from the disease, when treated with the same regimen. The chemotherapy regimens used in the disease have changed little for nearly 30 years. Although gene expression profiling has uncovered molecular subgroups that comprise this entity, little is known about mechanisms underlying these changes in gene expression. Thus far, a handful of studies have explored the role of mutations in DLBCL tumors. The advent of exon-capture technologies and high throughput sequencing provide new opportunities for the exome-wide identification of mutations that are most likely to result in altered gene and protein expression. Through in-solution exon-capture, we aim to perform an exome-wide screen for clinically relevant mutations that occur in at least 10% of patients. We strongly believe that this study will reveal new aspects of disease biology and potential therapeutic targets.

描述（由申请人提供）：弥漫性大B细胞淋巴瘤（DLBCL）是最常见的淋巴瘤形式，占所有非Hodgkin淋巴瘤病例的40％。该疾病表现出惊人的临床异质性。不到一半的患者用标准的多药化学疗法治愈。另一方面，当患者使用相同方案治疗时，患者以上的一半以上患者会出现早期进展，复发和死亡。该疾病中使用的化疗方案几乎没有变化近30年。尽管基因表达分析发现了构成该实体的分子亚组，但对基因表达中这些变化的基础机制知之甚少。到目前为止，少数研究探索了突变在DLBCL肿瘤中的作用。外显子捕获技术和高吞吐量测序的出现为外显域识别突变提供了新的机会，这些突变最有可能导致基因和蛋白质表达改变。通过插入外显子捕获，我们旨在对至少10％的患者进行临床相关突变进行外显屏筛查。我们坚信，这项研究将揭示疾病生物学和潜在治疗靶点的新方面。