Defining the genomic and microenvironmental features of diffuse large B cell lymphoma in HIV + patients (Biospecimens/Biocohort)

定义 HIV 患者弥漫性大 B 细胞淋巴瘤的基因组和微环境特征（生物样本/生物队列）

• 批准号: 10619709
• 负责人: Michael B Kastan
• 金额: $ 8.33万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10619709
• 关键词: AIDS related cancer; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Affect; Bioinformatics; Cells; Characteristics; Clinical; Collaborations; Data; Disease; Epidermal Growth Factor Receptor; Exhibits; Foundations; Funding; Gene Expression; Gene Expression Profile; Genetic; Genomic approach; Genomics; Goals; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Individual; Inferior; Institution; KRAS2 gene; Knowledge; Malignant Neoplasms; Methods; Molecular Probes; Mutation; Non-Hodgkin' s Lymphoma; Outcome; Outcome Study; Pathogenesis; Pathway interactions; Patient-Focused Outcomes; Patients; Pattern; Positioning Attribute; Prognostic Factor; Research Priority; Research Support; Resources; Risk; Sampling; Survival Rate; Therapeutic; United States National Institutes of Health; Virus Diseases; Work; antiretroviral therapy; base; co-infection; cohort; comorbidity; driver mutation; exome sequencing; experience; high risk; improved; improved outcome; innovation; large cell Diffuse non-Hodgkin' s lymphoma; novel therapeutic intervention; prognostic; recruit; response; single cell sequencing; single-cell RNA sequencing; targeted treatment; therapeutic target; transcriptome sequencing; tumor; tumor microenvironment

ABSTRACT HIV-positive patients are at high risk for developing diffuse large B cell lymphoma (DLBCL). Despite improved patient outcomes in the era of retroviral therapy, HIV-positive DLBCL patients continue to experience inferior survival compared to their HIV-negative counterparts. While the genetic origins and prognostic factors of DLBCL are increasingly well-defined, a similar understanding of the disease in HIV+ patients has been elusive. We have carried out a preliminary genomic analysis of HIV+ DLBCL patients that revealed key differences in mutation patterns. Additionally, we found differences in a previously described gene expression signature that reflects the tumor microenvironment and is strongly associated with poor survival. In this proposal, we seek to advance our understanding of the genetic and microenvironment features underlying DLBCL in HIV+ patients, particularly as they relate to outcome. Through a combination of genomics approaches in a well-powered patient cohort, we will comprehensively define the genetic alterations, gene expression patterns and microenvironment characteristics that distinguish HIV+ DLBCLs. This work will provide an important resource for the field and indicate therapeutic targets to improve outcomes in this disease, including approaches to disrupting the nexus between the tumor and the microenvironment.

摘要 HIV阳性患者发生弥漫性大B细胞淋巴瘤（DLBCL）的风险较高。尽管改善了 在逆转录病毒治疗的时代，HIV阳性DLBCL患者继续经历劣化， 与艾滋病毒阴性者相比，DLBCL的遗传起源和预后因素 虽然这些疾病的定义越来越明确，但对HIV+患者的疾病的类似理解一直难以捉摸。我们有 对HIV+ DLBCL患者进行了初步的基因组分析，揭示了突变的关键差异， 模式.此外，我们发现了先前描述的基因表达特征的差异，这些差异反映了 肿瘤微环境，并与生存率低密切相关。在这一建议中，我们寻求推进我们的 了解HIV+患者DLBCL的遗传和微环境特征，特别是 它们与结果有关。通过在一个动力良好的患者队列中结合基因组学方法，我们 将全面定义遗传改变、基因表达模式和微环境 区分HIV+ DLBCL的特征。这项工作将为该领域提供重要资源， 指出改善这种疾病结果的治疗目标，包括破坏这种关系的方法 在肿瘤和微环境之间。