Genetic Origins of Adverse Outcomes in African Americans with Lymphoma

非裔美国人淋巴瘤不良后果的遗传起源

基本信息

批准号：
10587289
负责人：
Sandeep Dave
金额：
$ 48.57万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-18 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10587289
关键词：
Address Affect African American African American population Age B-Lymphocytes BRAF gene Bioinformatics Caucasians Cell Lineage Cells Collaborations DNA Sequence Alteration DNA sequencing Data Development Diagnosis Disease Event Exhibits Foundations Gene Expression Gene Silencing Genes Genetic Genetic Heterogeneity Genomics Goals Health Services Accessibility Hematopoietic Neoplasms Incidence Inequity Institution KRAS2 gene Knock-out Knowledge Lymphoma Lymphomagenesis Malignant Neoplasms Methods Methyltransferase Gene Molecular Mutation Outcome Pathogenesis Patients Population Prognosis Proliferating Race Role Structure of germinal center of lymph node Therapeutic Therapeutic Intervention Time Work adverse outcome cohort driver mutation exome sequencing histone methyltransferase improved outcome in vivo in vivo Model innovation large cell Diffuse non-Hodgkin&apos s lymphoma loss of function overexpression recruit response socioeconomics targeted treatment transcriptome transcriptome sequencing tumor

项目摘要

ABSTRACT Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic heterogeneity. It has been known for some time that African American patients have poorer outcomes than Caucasian patients. After correcting for potential differences in socioeconomics and access to care, our data indicate that the poorer outcomes in African Americans arise primarily from distinct genetics of their tumors. The underlying genetic causes of these poorer outcomes have not been studied systematically. Here, we propose to investigate tumor and germline genetics of African Americans to comprehensively understand the genetic basis of their poorer outcomes. Preliminary genomic analysis of African American DLBCL patients has revealed more frequent mutations in histone methyltransferase genes and other genes. In this proposal, we seek to comprehensively define the genetic origins of poor outcomes in African Americans with DLBCL and perform functional characterization of selected genomic alterations.

抽象的弥漫性大B细胞淋巴瘤（DLBCL）是最常见的血液癌形式，其特征是遗传异质性的惊人程度。一段时间以来，非裔美国人患者有比白人患者的结局差。在纠正了社会经济学的潜在差异之后获得护理，我们的数据表明，非洲裔美国人的较差的结果主要来自不同肿瘤的遗传学。尚未研究这些较差结果的基本遗传原因系统地。在这里，我们建议调查非裔美国人的肿瘤和种系遗传学全面地了解其较差结果的遗传基础。初步基因组分析非裔美国人DLBCL患者显示，组蛋白甲基转移酶基因的突变更频繁和其他基因。在此提案中，我们试图全面定义不良结果的遗传起源具有DLBCL的非裔美国人并对选定的基因组改变进行功能表征。