Novel Approaches to Detect Virus-Cancer Associations

检测病毒与癌症关联的新方法

• 批准号: 6892194
• 负责人: PAUL G. AHLQUIST
• 金额: $ 35.28万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892194
• 关键词: Epstein Barr virus; biotechnology; breast neoplasms; clinical research; genetic techniques; head /neck neoplasm; human papillomavirus; human subject; microarray technology; patient oriented research; polymerase chain reaction; technology /technique development; virus DNA; virus RNA; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): Viruses are established, causal factors in 15%-20% of human cancers and are widely suspected to be involved in more. The long-range goals of this project are to develop methods to simultaneously screen tumor and other tissue samples for the genomes or partial genomes of many viruses, to use these methods to test for novel virus-cancer associations, and to determine their statistical and clinical significance. In particular, this highly collaborative proposal describes how a new, uniquely flexible, maskless photolithography technology will be used to produce and refine high density oligonucleotide microarrays able to sensitively detect all genes or transcripts of all known human tumor viruses. For comparison, arrays of PCR-amplified viral probes spotted on glass slides will also be tested. Additional experiments will systematically optimize extraction and amplification methods for specific, sensitive, and robust detection of viral RNA and DNA sequences at low copy number in clinical tissue samples. The resulting tools and methodology will be applied to relevant clinical samples to test and resolve the emerging connections of two well- characterized human tumor viruses, human papilloamavirus (HPV) and Epstein- Barr virus (EBV), with oral cancers and breast cancers, respectively, and to compare the microarray results with other state-of-the-art virus detection methods applied to the same tissue samples. These studies will provide proof- of-principle tests of microarray use in detecting and characterizing viral contributions to cancer and address significant, current issues in the viral etiology of specific tumors. Simultaneous microarray screening for many viruses o viral genotypes amplifies the power of etiologic and diagnostic studies on precious tissue samples, offers the potential to discover unsuspected virus-cancer links, and allows profiling expression of viral and selected cell genes to provide the molecular signatures of a tumor and to evaluate the potential contribution of the virus to that tumor. The methods developed also will be applicable to probe for virus involvement in other chronic or acute disorders.

描述（由申请人提供）：病毒是因果因素 在15％-20％的人类癌症中，被广泛怀疑参与更多。 该项目的远程目标是开发同时的方法 用于基因组或部分基因组的筛查肿瘤和其他组织样品 许多病毒，使用这些方法测试新的病毒结用者 关联，并确定其统计和临床意义。 特别是，这项高度协作的建议描述了一个新的， 独特的灵活，无面具的光刻技术将用于 生产和完善高密度寡核苷酸微阵列 敏感地检测所有已知人类肿瘤病毒的所有基因或转录本。 为了进行比较，在载玻片上发现了PCR放大病毒探针的阵列 也将进行测试。 其他实验将系统地优化 特异性，敏感和鲁棒的提取和扩增方法 在临床组织中低拷贝数的病毒RNA和DNA序列的检测 样品。 最终的工具和方法将应用于相关 临床样品测试和解决两个良好的新兴联系 表征了人类肿瘤病毒，人乳头瘤病毒（HPV）和爱泼斯坦 - Barr病毒（EBV），分别有口服癌症和乳腺癌，以及 将微阵列结果与其他最先进的病毒检测进行比较 应用于相同的组织样品的方法。 这些研究将提供证明 - 用于检测和表征病毒的微阵列的原则测试 对癌症的贡献并解决病毒的重大问题 特定肿瘤的病因。 许多人同时进行微阵列筛选 病毒o病毒基因型扩大了病因和诊断的力量 关于宝贵组织样品的研究，有可能发现的潜力 未经引起的病毒癌链接，允许病毒和 选定的细胞基因提供肿瘤的分子特征和至 评估病毒对该肿瘤的潜在贡献。 方法 开发的也将适用于探测病毒参与其他 慢性或急性疾病。