Exome-wide screening for common mutations in lymphoma

淋巴瘤常见突变的全外显子组筛查

• 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
• 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' 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' s lymphoma; molecular phenotype; novel therapeutics; outcome forecast; protein expression; response; therapeutic target; tumor

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，占所有非霍奇金淋巴瘤病例的近40%。该疾病表现出显著的临床异质性。不到一半的患者通过标准的多药物化疗治愈。另一方面，当用相同的方案治疗时，超过一半的患者经历疾病的早期进展、复发和死亡。近30年来，用于该病的化疗方案几乎没有变化。虽然基因表达谱揭示了分子亚组，包括这个实体，很少有人知道这些变化的基因表达的机制。到目前为止，一些研究已经探索了突变在DLBCL肿瘤中的作用。外显子捕获技术和高通量测序的出现为外显子组范围内鉴定最有可能导致基因和蛋白质表达改变的突变提供了新的机会。通过溶液中外显子捕获，我们的目标是对至少10%的患者中发生的临床相关突变进行外显子组范围的筛查。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。