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

摘要 HIV阳性患者患弥漫性大B细胞淋巴瘤(DLBCL)的风险很高。尽管情况有所改善 患者结局在逆转录病毒治疗时代，HIV阳性的DLBCL患者继续经历劣势 与艾滋病毒阴性的患者相比，他们的存活率更高。而DLBCL的遗传起源和预后因素 尽管人们对这种疾病的定义越来越明确，但对艾滋病毒+患者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，发现了突变的关键差异 模式。此外，我们发现前面描述的反映基因表达特征的基因表达特征存在差异 肿瘤微环境，并与低存活率密切相关。在这项提议中，我们寻求推进我们的 了解HIV阳性患者DLBCL的遗传和微环境特征，特别是AS 它们与结果有关。通过在一个实力雄厚的患者队列中结合基因组学方法，我们 将全面定义遗传变化、基因表达模式和微环境 区别HIV+DLBCL的特征。这项工作将为实地和 指出改善这种疾病结果的治疗目标，包括破坏神经联系的方法 肿瘤和微环境之间的关系。

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.