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年人类基因组项目完成以来，人们对将人类基因组信息直接转化为临床实践一直非常期望。在过去的几年中，许多大型研究已分类人类DNA变异。同时，DNA测序技术的进步增加了吞吐量和成本下降。现在，我们可以广泛地部署人类遗传变异的知识，再加上高通量DNA测序方法，以实现个性化的，大规模的“医学重新定位”，以全面揭示疾病的遗传机制并影响临床治疗。这种“基础对床边”翻译需要多学科研究。华盛顿大学是临床领域的领导者 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）和健康服务研究（Heagerty，Patrick，Regier和Veenstra）。在这个高度综合的建议中，我们结合了这些优势，以研究临床使用外部数据的各个方面。我们提出了一项对常规护理的随机对照试验，与华盛顿大学医学遗传学诊所患者的外显子分析的添加，他们对大肠癌/多兴趣/多息护物（CRCP）基因检测有临床指示。我们将评估该技术在识别临床相关的CRCP基因突变，成本和患者衍生的措施方面的有效性。在专家审议的审议后，我们还将将CLIA认证的结果退还给参与者。我们将获得结构化 RCT的通常护理和外部武器中的受试者的反馈，以评估他们的经验。我们将进一步考虑使用焦点小组的转诊医师和患者的输入。我们将调查需要返回CLIA认证研究结果的法律依据。我们工作的一个重要组成部分不仅确定要返回哪些结果，还确定了如何最好地将这些基因组数据纳入病历中。最后，我们将对没有可识别的CRCP突变的家庭进行CRCP基因发现研究。这种新型基因发现会影响预防和治疗。