Polyomavirus-Associated Human Cancers

描述（由申请人提供）：虽然多瘤病毒可以在细胞培养和动物模型中诱导细胞转化，但它们在引起人类癌症中的作用一直存在争议。这个家族的一个新成员，被命名为默克尔细胞多瘤病毒（MCV），在2008年初被报道为罕见的默克尔细胞癌（MCC）的潜在病原。随后，北美、欧洲和澳大利亚的样本证实了MCC中MCV的高发病率。MCV似乎存在于8-16%的对照样本中，在胃肠道和皮肤的各种组织中拷贝数非常低，而80%的默克尔细胞癌样本中存在MCV。这种现象在其他已知的人类致癌病毒中也有记载。此外，许多致癌病毒引起不止一种类型的癌症。例如，疱疹病毒-8 (HHV-8)/卡波西氏肉瘤疱疹病毒（KSHV）引起卡波西氏肉瘤、淋巴瘤等疾病。有趣的是，默克尔细胞癌和卡波西肉瘤具有相似的流行病学特征。因此，我们假设除了默克尔细胞瘤外，MCV还与其他癌症有关。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在不同类型癌症中的作用。我们的具体目标是1。开发用于血清流行病学研究的MCV免疫测定和用于癌症免疫组织化学分析的MCV特异性抗体。2. 用一种基于阵列的综合检测方法鉴定癌症中的多瘤病毒；3. 采用病例对照设计，建立初步的血清流行病学证据，支持或反对MCV作为一系列癌症的致病因子。一旦确定了病毒的病原学作用，我们将有可能将该病毒用作诊断和预后的生物标志物以及潜在的治疗靶点。这些长期目标已在其他致癌病毒（如乙型肝炎病毒和人乳头瘤病毒）中得到成功证明。

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.