CGH IN HIV+ AND HIV-PATIENTS WITH NHL

描述：(申请人描述)非霍奇金淋巴瘤(NHL) 在5%-10%的艾滋病毒阳性个体中发生。增加的发病率 HIV淋巴肿大、组织学分级/分期与临床病程 淋巴瘤阳性患者提示一种更具侵袭性的恶性疾病 而不是HIV阴性的患者。然而，病原学和分子事件 导致淋巴增生症的定义并不明确。目前还不清楚是否 恶性细胞的发展和/或侵袭性仅仅是由于 个人的免疫功能受损状态或免疫功能是否受损 状态导致的淋巴瘤在基因上与那些 在没有接触艾滋病毒的情况下发展。复杂而独特的分子 细胞遗传学异常是侵袭性癌症的特征。这个 研究人员假设，艾滋病毒感染促进了 在基因上不同于 自发性淋巴瘤。比较基因组杂交(CGH)允许 对发生在肿瘤中的分子细胞遗传学变化的全基因组调查。 他们将确定CGH是否区分非霍奇金淋巴瘤 (非霍奇金淋巴瘤)在HIV阳性和HIV阴性患者中。飞行员的目标是 建议对20例HIV淋巴瘤标本进行CGH分析 与20级匹配的HIV阴性患者建立 组织样本提取和基因组分析的可行性并获得 支持更大规模研究的科学价值的初步数据。这个 试验计划的具体目标是：(1)收集组织样本，用于 在这项试点研究中使用，并确定收集它们用于 更大规模的研究。EB病毒感染与淋巴瘤的分子特征 单克隆性将通过聚合酶链式反应和Southern印迹来测量，以便仔细 HIV阳性和HIV阴性病例的匹配，(2)确定是否 不同的基因组变化区别于从HIV获得的淋巴瘤 HIV阳性和阴性患者，(3)发展快速、半自动 计算全息促进大种群基因组分析的方法。

DESCRIPTION: (Applicant's Description) Non-Hodgkin's lymphoma (NHL) develops in 5-10% of HIV positive individuals. The elevated incidence of lymphomagenesis, histologic grade/stage and the clinical course of HIV positive patients with lymphoma suggests a more aggressive malignant disease than in HIV negative patients. However, the etiology and molecular events leading to lymphomagenesis are poorly defined. It is unclear whether the development and/or aggressiveness of malignant cells is due simply to the immunocompromised status of the individual or whether the immunocompromised status results in lymphomas that are genetically different from those that develop in the absence of HIV exposure. Complex and distinctive molecular cytogenetic aberrations are hallmarks of aggressive cancers. The investigators hypothesize that HIV infection facilitates emergence of premalignant and malignant clones that are genetically distinctive from spontaneous lymphomas. Comparative genomic hybridization (CGH) allows genome-wide surveys of molecular cytogenetic changes that occur in tumors. They will determine whether CGH discriminates between non-Hodgkin's lymphoma (NHL) in HIV positive and HIV negative patients. The goal of the pilot proposal is to perform CGH analyses on lymphoma specimens from 20 HIV positive and 20 grade matched HIV negative patients to establish the feasibility of tissue sample retrieval and genomic analysis and to obtain preliminary data to support the scientific merit of a larger study. The specific aims of the pilot project are to: (1) collect tissue samples for use in this pilot study and determine feasibility of collecting them for a larger study. Molecular characterization of EBV presence and lymphoma monoclonality will be measured by PCR and Southern blot to allow careful matching of HIV positive and HIV negative cases, (2) determine whether distinctive genomic changes discriminate between lymphomas obtained from HIV positive and HIV negative patients, (3) develop rapid, semi-automated approaches for CGH to facilitate genomic analysis of large populations.