Clinical sequencing in cancer: Clinical ethical and technological studies

癌症临床测序：临床伦理和技术研究

• 批准号: 8776958
• 负责人: Gail Pairitz Jarvik
• 金额: $ 208.92万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-05 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8776958
• 关键词: Base Pairing; Bioethics; Cataloging; Catalogs; Clinic; Clinical; Clinical Medicine; Clinical Treatment; Colorectal Cancer; Coupled; DNA Resequencing; DNA Sequence; Data; Disease; Effectiveness; Ethics; Family Study; Feedback; Focus Groups; Gene Mutation; Generations; Genetic; Genetic Variation; Genetic screening method; Genomics; Health Services Research; High-Throughput DNA Sequencing; Human; Human Genetics; Human Genome Project; Incidental Findings; Knowledge; Legal; Malignant Neoplasms; Measures; Medical; Medical Genetics; Medical Informatics; Medical Records; Methods; Mutation; Participant; Patients; Physicians; Positioning Attribute; Prevention; Randomized Controlled Trials; Research; Resolution; Structure; Technology; Translating; Translations; Trinidad; Universities; Variant; Washington; Work; arm; base; clinical sequencing; clinically relevant; cost; exome; expectation; experience; gene discovery; genetic disorder diagnosis; human DNA; multidisciplinary; novel; polyposis; treatment as usual

DESCRIPTION (provided by applicant): Since the completion of the Human Genome Project in 2001, there have been great expectations for translating human genomic information directly into clinically practice. During the last several years, numerous large studies have cataloged human DNA variation. In parallel, advances in DNA sequencing technologies have increased the throughput and decreased costs. We are now positioned to broadly deploy our knowledge of human genetic variation, coupled with high-throughput DNA sequencing methods, for individualized, large-scale "medical resequencing" to comprehensively reveal the genetic mechanisms underlying disease and influence clinical treatment. This "base pairs to bedside" translation requires multidisciplinary study. The University of Washington is a leader in clinical genetics (Bennett, Burke, Byers, Hisama, and Jarvik, Motulsky, Raskind, and Sybert), bioethics (Burke, Jarvik, Fullerton, and Trinidad), second-generation sequencing, variant calling and annotation (Rieder and Nickerson), disease gene discovery (Browning, Heagerty, Jarvik, Nickerson, and Rieder), medical informatics (Tarczy-Hornoch), and health services research (Heagerty, Patrick, Regier, and Veenstra). In this highly integrated proposal, we combine these strengths to investigate aspects of using exomic data clinically. We propose a randomized controlled trial of usual care vs. the addition of exome analysis in University of Washington Medical Genetics Clinic patients who have clinical indications for colorectal cancer/polyposis (CRCP) genetic testing. We will evaluate the effectiveness of this technology for the identification of clinically relevant CRCP gene mutations, cost, and patient derived measures. After deliberations by experts to identify variants that are incidental findings that should be returned, we will also return CLIA certified results to the participants. We will obtain structured feedback from subjects in both the usual care and exome arms of the RCT to evaluate their experiences. We will further consider the input of referring physicians and patients using focus groups. We will investigate the legal basis of the need to return CLIA certified research results. An important component of our work is determination of not only which results to return, but how best to incorporate these genomic data into the medical record. Finally, we will perform CRCP gene discovery studies for families without identifiable CRCP mutations; such novel gene discovery can impact prevention and treatment.

描述（由申请人提供）：自2001年人类基因组计划完成以来，人们对将人类基因组信息直接转化为临床实践寄予厚望。在过去的几年里，许多大型研究已经对人类DNA变异进行了编目。与此同时，DNA测序技术的进步提高了通量，降低了成本。我们现在的定位是广泛运用我们的人类遗传变异知识，结合高通量DNA测序方法，进行个性化、大规模的“医学重测序”，全面揭示疾病的遗传机制，影响临床治疗。这种“碱基对到床边”的转换需要多学科的研究。华盛顿大学在临床医学方面处于领先地位