Polyomavirus- Associated Human Cancers

多瘤病毒相关人类癌症

• 批准号: 7897082
• 负责人: Yu-Tsueng Liu
• 金额: $ 20.16万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7897082
• 关键词: Adult; Animal Model; Animals; Antibodies; Antigens; Australia; Biological Assay; Biological Markers; Blood; CDKN2A gene; Cancer Center; Cancer Etiology; Cancer Patient; Case-Control Studies; Cell Culture Techniques; Cells; Chronic Lymphocytic Leukemia; Collection; Consent; Controlled Study; Cross-Sectional Studies; Cutaneous; DNA; Development; Diagnostic; Disease; Epidemiologic Studies; Epidemiology; Europe; Family member; Gastrointestinal Neoplasms; Gastrointestinal tract structure; General Population; Goals; Hand; Hepatitis B; Hepatitis B Virus; Hepatitis C; Herpesviridae; Human; Human Herpesvirus 4; Human Herpesvirus 8; Human Papillomavirus; Human T-lymphotropic virus 1; Human Virus; Immunoassay; Immunohistochemistry; Immunosuppression; Incidence; Infection; Kaposi Sarcoma; Large T Antigen; Link; Lung; Lymphoma; Malignant Neoplasms; Malignant neoplasm of prostate; Merkel Cells; Merkel cell carcinoma; Molecular; Names; North America; Oncogenic; Oncogenic Viruses; Outcome; Pathology; Patients; Plasma; Plasmacytic Leukemia; Play; Polyomavirus; Predisposing Factor; Primary carcinoma of the liver cells; Prognostic Marker; Reagent; Reporting; Research; Research Ethics Committees; Resource Sharing; Resources; Role; Sampling; Screening procedure; Second Primary Cancers; Seroepidemiologic Studies; Serological; Serum; Skin; Source; Staining method; Stains; Sun Exposure; T-Lymphocyte; Testing; Tissue Array Research Program; Tissue Microarray; Tissues; Tumor Antibodies; Tumor Tissue; Virus; Virus Integration; base; biobank; cancer prevention; cancer type; case control; cell transformation; cohort; design; experience; high risk; interest; malignant breast neoplasm; neoplastic cell; patient population; prognostic; public health relevance; therapeutic target; tumor; vaccine development

DESCRIPTION (provided by applicant): While polyomaviruses can induce cell transformation in cell culture and in animal models, their role in causing human cancers has been controversial. A new member of this family, named Merkel cell polyomavirus (MCV) was reported to be a potential etiological agent for the rare Merkel cell carcinoma (MCC) in early 2008. Subsequently, high incidence of MCV in MCC was confirmed with samples from North America, Europe and Australia. MCV appears to be present in 8-16% of control samples with very low copy number in various tissues of gastrointestinal tract and skin, compared to 80% of Merkel cell cancer samples. Such phenomenon is also documented in other known human oncogenic viruses. In addition, a number of oncogenic viruses cause more than one type of cancer. For example, herpesvirus-8 (HHV-8)/Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma, lymphoma and other diseases. Interestingly, Merkel cell carcinoma and Kaposi's sarcoma share a similar epidemiological profile. Therefore, we hypothesize that MCV is also associated with other cancers in additional to the Merkel cell tumor. We are also interested in finding if the other known and unknown polyomaviruses are also associated with cancer development. To achieve these goals, we will create a variety of reagents and assays to determine the involvement of human polyomaviruses, particularly MCV, in different types of cancers. Our specific aims are 1. Developing MCV immunoassays for seroepidimiological studies and MCV-specific antibodies for cancer immunohistochemical analyses. 2. Identifying polyomaviruses in cancer with a comprehensive array-based assay; 3. Using a case-control design, establish preliminary seroepidemiologic evidence for or against MCV as a causal agent in a spectrum of cancers. Once establishing the etiological role of the virus, we will potentially use this virus as a diagnostic and prognostic biomarker and as a potential therapeutic target. These longer term goals have been successfully demonstrated in other oncogenic viruses, such as hepatitis B virus and human papillomaviruses. PUBLIC HEALTH RELEVANCE: Polyomavirus- Associated Human Cancers A recently discovered virus, named Merkel cell polyomavirus (MCV), may become the 7th bona fide human cancer-causing virus. This study aims to investigate the association of this virus and various types of cancer and to evaluate the use of this virus as a diagnostic and prognostic marker. A potential long term goal is to develop a vaccine targeting MCV for cancer prevention.

描述（由申请人提供）：虽然多瘤病毒可以在细胞培养物和动物模型中诱导细胞转化，但其在引起人类癌症中的作用一直存在争议。2008年初，该家族的一个新成员，命名为默克尔细胞多瘤病毒（MCV），被报道是罕见的默克尔细胞癌（MCC）的潜在病原体。随后，来自北美、欧洲和澳大利亚的样本证实了MCC中MCV的高发病率。与80%的默克尔细胞癌样品相比，MCV似乎存在于8-16%的对照样品中，在胃肠道和皮肤的各种组织中具有非常低的拷贝数。这种现象在其他已知的人类致癌病毒中也有记载。此外，许多致癌病毒引起一种以上的癌症。例如，疱疹病毒-8（HHV-8）/卡波西肉瘤疱疹病毒（KSHV）引起卡波西肉瘤、淋巴瘤和其他疾病。有趣的是，默克尔细胞癌和卡波西肉瘤有着相似的流行病学特征。因此，我们假设MCV也与除默克尔细胞瘤之外的其他癌症相关。我们也有兴趣发现其他已知和未知的多瘤病毒是否也与癌症的发展有关。为了实现这些目标，我们将创建各种试剂和检测方法，以确定人类多瘤病毒，特别是MCV，在不同类型的癌症中的参与。我们的具体目标是1。开发MCV免疫测定法用于血清流行病学研究和MCV特异性抗体用于癌症免疫组织化学分析。2.用全面的基于阵列的测定法鉴定癌症中的多瘤病毒; 3.采用病例对照设计，建立支持或反对MCV作为一系列癌症致病因子的初步血清流行病学证据。一旦确定了病毒的病因学作用，我们将有可能使用这种病毒作为诊断和预后生物标志物，并作为潜在的治疗靶点。这些长期目标已在其他致癌病毒中得到成功证实，如B型肝炎病毒和人乳头瘤病毒。 公共卫生关系：最近发现的一种名为默克尔细胞多瘤病毒（MCV）的病毒可能成为第七种真正的人类致癌病毒。本研究旨在调查该病毒与各种类型癌症的关联，并评估该病毒作为诊断和预后标志物的用途。一个潜在的长期目标是开发一种靶向MCV的癌症预防疫苗。