Genomic profiling of AIDS-related Plasmablastic lymphoma

艾滋病相关浆母细胞淋巴瘤的基因组分析

• 批准号: 7101805
• 负责人: Chung-Che Chang
• 金额: $ 17.72万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-27 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7101805
• 关键词: B cell lymphoma; artificial chromosomes; clinical research; comparative genomic hybridization; disease /disorder classification; fluorescent in situ hybridization; genetic polymorphism; genome; high throughput technology; human immunodeficiency virus; human tissue; immunocytochemistry; lymphoma; mouth neoplasms; multiple myeloma; neoplasm /cancer genetics; proteomics; virus genetics; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): Plasmablastic lymphoma (PL), one of the most frequent oral malignancies in human immunodeficiency virus (HIV) infected patients, has very poor prognosis despite the use of highly active antiretroviral therapy (HAART) and standard chemotherapy for diffuse large B-cell lymphoma (CHOP based regimen). Importantly, the incidence of PL has significantly increased following the introduction of HAART. By WHO Classification, PL is categorized as a subtype of diffuse large B-cell lymphoma (DLBCL) which is notably associated with HIV and Epstein Barr virus. We hypothesize that a significant subset, if not all, of PL is biologically more like plasma cell myelomas (PCM) than DLBCL. In preliminary studies, we have shown that PL and PCM share almost indistinguishable immunophenotypic expression profiles. As the initial step to test our hypothesis, the main goal of this R21 proposal is to evaluate the genetic similarities and differences among AIDS-related PL, DLBCL (AIDS-related and non AIDS-related) and PCM. We will apply array-based comparative genomic hybridization (array CGH) technology, recently developed by us and others, allowing the high-throughput analysis of DNA copy number aberrations, to determine the genomic profiles of these tumors. The findings at the genome level will then be preliminarily examined at proteome levels. If the results of this proposed study support our hypothesis, we will confirm these findings in the next phase (an R01 grant application) of study with a larger sample size. If our hypothesis is substantiated in the next phase of study, a subset of patients with AIDS-related PL may be considered for the therapeutic regimens against PCM to improve treatment outcome. Building on the findings of the first genome-wide analysis of AIDS-related PL outlined in this proposal, our long-term goals are: 1) to elucidate the pathogenesis of AIDS-related PL, 2) to identify reliable diagnostic and prognostic biomarkers useful for detection of AIDS-related PL and its progression and 3) to develop novel agents for targeted therapies to prevent and/or treat PL. Ultimately, we may be able to eliminate suffering of AIDS patients from this currently deadly disease.

描述（由申请人提供）：浆母细胞淋巴瘤（PL）是人类免疫缺陷病毒（HIV）感染患者中最常见的口腔恶性肿瘤之一，尽管使用高效抗逆转录病毒疗法（HAART）和弥漫性大B细胞淋巴瘤的标准化疗（基于CHOP的方案），但其预后非常差。重要的是，HAART 引入后 PL 的发生率显着增加。根据 WHO 分类，PL 被归类为弥漫性大 B 细胞淋巴瘤 (DLBCL) 的一种亚型，该亚型与 HIV 和 Epstein Barr 病毒密切相关。我们假设 PL 的一个重要子集（如果不是全部）在生物学上更像浆细胞骨髓瘤 (PCM)，而不是 DLBCL。在初步研究中，我们发现 PL 和 PCM 具有几乎无法区分的免疫表型表达谱。 作为检验我们假设的第一步，R21 提案的主要目标是评估艾滋病相关 PL、DLBCL（艾滋病相关和非艾滋病相关）和 PCM 之间的遗传相似性和差异。我们将应用我们和其他人最近开发的基于阵列的比较基因组杂交（阵列 CGH）技术，允许对 DNA 拷贝数畸变进行高通量分析，以确定这些肿瘤的基因组图谱。基因组水平的发现随后将在蛋白质组水平进行初步检查。如果这项拟议研究的结果支持我们的假设，我们将在下一阶段（R01 拨款申请）研究中以更大的样本量确认这些发现。如果我们的假设在下一阶段的研究中得到证实，则可以考虑对 AIDS 相关 PL 患者的子集进行针对 PCM 的治疗方案，以改善治疗结果。基于本提案中概述的首次对艾滋病相关 PL 进行全基因组分析的结果，我们的长期目标是：1) 阐明艾滋病相关 PL 的发病机制，2) 确定可用于检测艾滋病相关 PL 及其进展的可靠诊断和预后生物标志物，3) 开发用于预防和/或治疗 PL 的靶向治疗的新型药物。最终，我们也许能够消除艾滋病患者因这种目前致命的疾病而遭受的痛苦。

项目成果

Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH): revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma.

使用阵列比较基因组杂交（ACGH）对浆膜淋巴瘤的基因组分析：揭示了具有弥漫性大B细胞淋巴瘤的显着重叠基因组病变。

• DOI: 10.1186/1756-8722-2-47
• 发表时间: 2009-11-12
• 期刊: Journal of hematology & oncology
• 影响因子: 28.5
• 作者: Chang CC;Zhou X;Taylor JJ;Huang WT;Ren X;Monzon F;Feng Y;Rao PH;Lu XY;Fabio F;Hilsenbeck S;Creighton CJ;Jaffe ES;Lau CC
• 通讯作者: Lau CC