Molecular profiling of HIV-associated lymphoma in the US and Malawi

美国和马拉维 HIV 相关淋巴瘤的分子谱分析

• 批准号: 8603475
• 负责人: Satish Gopal
• 金额: $ 15.77万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-20 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603475
• 关键词: AIDS-Related Lymphoma; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Africa South of the Sahara; Area; Award; B-Lymphocytes; Biological; Biology; CD4 Lymphocyte Count; Categories; Cause of Death; Cells; Cessation of life; Clinical; Clinical Data; Clinical Research; Cohort Studies; Collaborations; Communicable Diseases; Data; Data Analyses; Diagnosis; Diffuse; Disease; Epidemiologic Studies; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Formalin; Funding; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; HIV; Hematology; Heterogeneity; Histologic; Histology; Hodgkin Disease; Individual; Infection; Inferior; Lead; Literature; Lymphoma; Lymphomagenesis; Lymphoproliferative Disorders; Malawi; Malignant Neoplasms; Medicine; Molecular; Molecular Profiling; Morbidity - disease rate; Observational Study; Oncogenic; Outcome; Paraffin Embedding; Patients; Persons; Population; Principal Investigator; RNA; Research; Research Personnel; Resources; Signal Transduction; Specimen; Supportive care; System; Techniques; The Cancer Genome Atlas; Therapeutic; Transplantation; Tumor Biology; United States; United States National Institutes of Health; Universities; Variant; Viral; Vulnerable Populations; Work; antiretroviral therapy; base; chemotherapy; cohort; comparative; disability; improved; insight; interest; mortality; next generation sequencing; oncology; professor; prognostic; programs; prospective; public health relevance; therapeutic target; therapy design; tool

DESCRIPTION (provided by applicant): This is an application for a National Institutes of Health Research on Malignancies in the Context of HIV/AIDS R21 award for Dr. Satish Gopal, a Clinical Assistant Professor of Medicine in Hematology-Oncology and Infectious Diseases at UNC-Chapel Hill, who is based at the university's longstanding research collaboration in Malawi. Dr. Gopal is establishing himself as a young investigator in the area of HIV-associated lymphoma, and also lymphoma treatment in sub-Saharan Africa. This award will provide Dr. Gopal and his co- investigators with the support necessary to undertake the most comprehensive genomic assessment of HIV- associated lymphoma performed to date. Lymphoma is a major cause of morbidity and mortality among HIV-infected individuals in both the US and sub-Saharan Africa. Despite being curable, outcomes in both settings remain inferior to HIV-uninfected individuals. To illuminate lymphoma biology in the context of HIV, this proposal takes advantage of a combination of strengths highly unique to UNC, including participation in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS), the highly successful UNC Project-Malawi clinical research program in Lilongwe, and inclusion as one of seven Data Analysis Centers for The Cancer Genome Atlas project. The proposed research additionally builds on two ongoing NIH-funded studies for which Dr. Gopal serves as principal investigator, including a large observational study of ~500 patients with HIV-associated lymphoma in CNICS, and a prospective lymphoma cohort study in Malawi. In Aim 1, the proposed research will compare genomic features using next-generation sequencing for HIV-associated lymphoma specimens occurring before and after antiretroviral therapy (ART). In Aim 2, comparisons will be made between the US and Malawi after adjustment for histology and ART status. Genomic characterizations will be done using RNAseq analyses of formalin-fixed paraffin embedded (FFPE) lymphoma specimens. These analyses will be used to define gene expression profiles (GEP) of diffuse large B-cell, Burkitt, and Hodgkin lymphoma specimens. GEP data will be compared between pre-ART and post-ART specimens, as well as between the United States and Malawi, using multivariable regression with expression variation as the outcome. The proposed research represents an important contribution to the existing literature in that GEP for lymphomas occurring specifically in the context of HIV have not previously been examined. Additionally, this work will allow for a comparative understanding of lymphoma biology in the US and Malawi, as well as before and after ART. The molecular insights gained will substantially illuminate lymphoma biology in the context of HIV, and result in improved treatments for this challenging and vulnerable population in both resource-rich and resource-limited settings.

描述（由申请人提供）：这是美国国立卫生研究院在艾滋病毒/艾滋病R21奖的背景下对恶性肿瘤的研究申请，Satish Gopal博士是北卡罗来纳大学教堂山分校血液肿瘤学和传染病医学的临床助理教授，他是该大学在马拉维的长期研究合作。Gopal博士是艾滋病毒相关淋巴瘤领域的年轻研究者，也是撒哈拉以南非洲淋巴瘤治疗的研究者。该奖项将为戈帕尔博士和他的合作研究者提供必要的支持，以进行迄今为止对艾滋病毒相关淋巴瘤进行的最全面的基因组评估。 淋巴瘤是美国和撒哈拉以南非洲地区HIV感染者发病和死亡的主要原因。尽管可以治愈，但这两种情况下的结果仍然不如未感染艾滋病毒的人。为了在艾滋病毒的背景下阐明淋巴瘤生物学，该提案利用了艾滋病研究中心独特的优势，包括参与艾滋病研究中心综合临床系统网络（CNICS），非常成功的马拉维临床研究项目，并作为癌症基因组图谱项目的七个数据分析中心之一。这项拟议的研究还建立在两项正在进行的NIH资助的研究基础上，Gopal博士担任主要研究者，包括一项在CNICS中对约500名HIV相关淋巴瘤患者进行的大型观察性研究，以及一项在马拉维进行的前瞻性淋巴瘤队列研究。在目标1中，拟议的研究将使用下一代测序方法比较抗逆转录病毒治疗（ART）前后发生的HIV相关淋巴瘤标本的基因组特征。在目标2中，将在调整组织学和ART状态后对美国和马拉维进行比较。将使用福尔马林固定石蜡包埋（FFPE）淋巴瘤标本的RNAseq分析进行基因组表征。这些分析将用于定义弥漫性大B细胞、伯基特和霍奇金淋巴瘤标本的基因表达谱（GEP）。GEP数据将在ART前和ART后标本之间进行比较，以及在美国和马拉维之间进行比较，使用表达变化作为结果的多变量回归。拟议的研究是对现有文献的重要贡献，因为以前没有研究过专门在艾滋病毒背景下发生的淋巴瘤的GEP。此外，这项工作将允许在美国和马拉维的淋巴瘤生物学的比较了解，以及之前和之后ART.所获得的分子见解将大大照亮淋巴瘤生物学在艾滋病毒的背景下，并导致在资源丰富和资源有限的环境中改善治疗这一具有挑战性和脆弱的人群。