IDENTIFYING NOVEL VIRUSES IN HUMAN MALIGNANCY

描述（由申请人提供）：对病毒感染与癌症之间联系的日益认识和理解，通过提供新的药物/疫苗靶点的可能性，显著影响了癌症的治疗和预防；然而，由于缺乏先进的高通量分子病毒学技术和可获得的全面和充分表征的癌症组织，进一步推进病毒性癌症研究的努力受到了阻碍。为了解决这一问题，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试点计划”包括呼吁开发靶向高通量病毒筛选，使用已被表征为基因组改变的肿瘤。因此，本提案的总体目标是应用一种创新的、简化的方法，以促进在癌症基因组图谱（TCGA）项目的特征良好的标本中发现以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的病毒特征，最终目标是为未来研究病毒感染与所有人类恶性肿瘤之间的联系奠定基础。因此，本提案的具体目的是：1)利用共识PCR和简并引物PCR，在现有的TCGA标本中寻找逆转录病毒。2)利用泛病毒微阵列平台，筛选已知和未知病毒，从所有已知的病毒科，我们将探索TCGA标本的病毒序列。3)利用序列独立测序方法和宏基因组分析，探索TCGA标本中存在高度分化病毒和来自以前未知病毒科的病毒的可能性。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，为癌症治疗和预防新疗法的潜在发展铺平道路。

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.