Defining the Functional Role of Mutations in Diffuse Large B cell Lymphoma

定义突变在弥漫性大 B 细胞淋巴瘤中的功能作用

• 批准号: 9040901
• 负责人: Sandeep Dave
• 金额: $ 51.05万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9040901
• 关键词: Accounting; B-Cell Lymphomas; B-Lymphocytes; CRISPR screen; Cell Line; Cells; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; DNA Sequence Alteration; Disease; Employee Strikes; Exclusion; Focal Adhesions; Gene Expression; Gene Expression Profiling; Gene Mutation; Genes; Genetic; Genetic Engineering; Genetic Heterogeneity; Goals; Health; Heterogeneity; Human; In Vitro; Individual; Knockout Mice; Link; Lymphoma; Malignant Neoplasms; Methods; Molecular Profiling; Mutate; Mutation; Outcome; Pathway interactions; Patients; Pattern; Play; Process; Research; Role; Sampling; Structure of germinal center of lymph node; Subgroup; Testing; Variant; Work; clinical phenotype; clinically significant; cohort; cost effective; exome sequencing; in vivo; large cell Diffuse non-Hodgkin' s lymphoma; loss of function; neoplastic cell; new therapeutic target; next generation sequencing; novel; novel therapeutics; therapeutic target; tumor; whole genome

 DESCRIPTION (provided by applicant): Diffuse Large B-Cell Lymphoma (DLBCL) is the most common form of lymphoma, comprising nearly 30% of all lymphoma cases. DLBCL is both clinically and molecularly heterogeneous. While nearly half of the patients are cured with standard therapy, the majority of the remaining patients succumb to the disease. In this proposal, we develop several complementary approaches that allow us to connect the specific genetic mutations in lymphomas to their context-specific roles. We propose to define the association of individual alterations with outcome, while accounting for the genetic heterogeneity among tumors. We have previously identified GNA13 as a commonly mutated gene in germinal center derived lymphomas including a subset of DLBCLs. We further propose to define lymphoma-specific roles of GNA13, as well as other variants that will be identified with this larger sample cohort through in vitro and in vivo approaches.

 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，占所有淋巴瘤病例的近30%。DLBCL在临床上和分子上都是异质性的。虽然近一半的患者通过标准治疗治愈，但其余大多数患者死于疾病。在这项提案中，我们开发了几种互补的方法，使我们能够将淋巴瘤中的特定基因突变与其特定的作用联系起来。我们建议定义个体改变与结果的关联，同时考虑肿瘤之间的遗传异质性。我们以前已经确定GNA13作为一个常见的突变基因在生殖中心衍生的淋巴瘤，包括一个子集的DLBCL。我们进一步提出定义GNA13的淋巴瘤特异性作用，以及将通过体外和体内方法用该较大样本队列鉴定的其他变体。