IDENTIFYING NOVEL VIRUSES IN HUMAN MALIGNANCY

描述（申请人提供）：对病毒感染与癌症之间联系的认识和理解不断增长，通过提供新药物/疫苗靶点的可能性，对癌症治疗和预防产生了重大影响;但是，在此情况下，进一步推进病毒性癌症研究的努力受到以下因素的阻碍：1）复杂的高通量分子病毒学技术的缺乏;可获得的全面和良好表征的癌组织。为了解决这个问题，NCI“在癌症基因组中生殖系和体细胞变化的大规模研究中识别潜在的病毒特征”包括呼吁使用已表征基因组改变的选定肿瘤开发靶向高通量病毒筛选。因此，本提案的总体目标是应用创新的、简化的方法，以促进在癌症基因组图谱（TCGA）项目的充分表征的标本中发现先前未识别的病毒关联。我们的试点工作将利用高度创新的技术来识别新的和新颖的病毒特征，最终目标是为未来的研究奠定基础，以调查病毒感染和所有人类恶性肿瘤之间的联系。因此，本研究的具体目的是：1）利用通用引物和简并引物PCR技术，在现有的TCGA标本中寻找逆转录病毒。2)使用泛病毒微阵列平台，它有能力从所有公认的病毒家族中筛选已知和未知的病毒，我们将探索TCGA标本的病毒序列。3)使用序列独立测序方法和宏基因组分析，我们将探讨高度不同的病毒和病毒从以前未知的病毒家族可能存在于TCGA标本的可能性。总的来说，这三种不同但互补的方法将进一步加深我们对病毒-癌症关联的理解，为癌症治疗和预防的新疗法的潜在开发铺平道路。 公共卫生相关性：这项研究利用了全球病毒预测公司（Global Viral Forecasting Inc）组建的世界级病毒发现实验室网络，首次系统地将新的分子技术应用于人类恶性肿瘤中病毒的发现。通过利用一个全面的战略，对病毒的发现沿着随着高品质的标本，从癌症基因组图谱（TCGA）项目，拟议的研究计划集建立一个框架，大规模的系统性合作与NCI发现与人类恶性肿瘤相关的病毒的全部范围。

DESCRIPTION (provided by applicant): A growing appreciation and understanding of the link between viral infections and cancer has significantly influenced cancer treatment and prevention by offering the possibility of new drug/vaccine targets; however, efforts to further advance viral cancer research have been hampered by the lack of 1) sophisticated high throughput molecular virology technologies and 2) accessible comprehensive and well characterized cancer tissues. To address this issue, the NCI "Identifying Potential Viral Signatures in Large Scale Studies of Germline and Somatic Changes in Cancer Genomes Pilot Program" includes calls for the development of targeted high throughput viral screening using selected tumors that have been characterized for genomic alterations. As such, the overall objective of this proposal is to apply an innovative, streamlined approach to facilitate the discovery of previously unidentified viral associations in the well-characterized specimens of The Cancer Genome Atlas (TCGA) project. Our pilot effort will utilize highly innovative techniques to identify new and novel viral signatures, with the ultimate goal of forming the basis for future studies to investigate the link between viral infection and all human malignancies. Accordingly, the specific aims of this proposal are: 1) Using consensus and degenerate primer PCR, we will search for retroviruses in available TCGA specimens. 2) Using a pan-viral microarray platform, which has the ability to screen for known and unknown viruses from all recognized viral families, we will explore the TCGA specimens for viral sequences. 3) Using sequence independent sequencing methods and metagenomic analysis, we will explore the possibility that highly divergent viruses and viruses from previously unknown viral families may exist within TCGA specimens. Overall, these three distinct but complimentary approaches will further our understanding of viral-cancer associations paving the way for the potential development of new therapeutics for cancer treatment and prevention. PUBLIC HEALTH RELEVANCE: The research proposed here utilizes a world class viral discovery laboratory network assembled by Global Viral Forecasting Inc, to, for the first time systematically apply novel molecular techniques to the discovery of viruses in human malignancies. By utilizing a comprehensive strategy toward viral discovery along with the high quality specimens from The Cancer Genome Atlas (TCGA) project, the proposed research program sets to establish a framework for large-scale systematic collaboration with NCI to discover the full range of viruses associated with human malignancy.