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: 8393217
• 负责人: Gail Pairitz Jarvik
• 金额: $ 212.18万
• 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 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8393217
• 关键词: Base Pairing; Bioethics; Cataloging; Catalogs; Clinic; Clinical; Clinical Medicine; Clinical Treatment; Colorectal Cancer; Coupled; DNA Resequencing; DNA Sequence; Data; Diagnosis; Disease; Effectiveness; Ethics; Family Study; Feedback; Focus Groups; Gene Mutation; Generations; Genetic; Genetic Variation; Genetic screening method; Genomics; Health Services Research; 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; clinically relevant; cost; exome; expectation; experience; gene discovery; 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抱有很大的期望。在过去的几年里，大量的大型研究对人类 DNA 变异进行了分类。与此同时，DNA 测序技术的进步提高了通量并降低了成本。我们现在的定位是广泛运用人类遗传变异知识，结合高通量DNA测序方法，进行个体化、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”的翻译需要多学科研究。华盛顿大学在临床医学领域处于领先地位 遗传学（Bennett、Burke、Byers、Hisama 和 Jarvik、Motulsky、Raskind 和 Sybert）、生物伦理学（Burke、Jarvik、Fullerton 和 Trinidad）、第二代测序、变异调用和注释（Rieder 和 Nickerson）、疾病基因发现（Browning、Heagerty、Jarvik、Nickerson 和 Rieder）、医学信息学（Tarczy-Hornoch）和卫生服务研究（Heagerty、Patrick、Regier 和 Veenstra）。在这个高度集成的提案中，我们结合了这些优势来研究临床使用外显子组数据的各个方面。我们建议对具有结直肠癌/息肉病 (CRCP) 基因检测临床指征的华盛顿大学医学遗传学诊所患者进行常规护理与外显子组分析的随机对照试验。我们将评估该技术在识别临床相关 CRCP 基因突变、成本和患者衍生指标方面的有效性。经过专家审议确定应返回的偶然发现的变异后，我们还将向参与者返回 CLIA 认证的结果。我们将获得结构化的 来自随机对照试验的常规护理和外显子组受试者的反馈，以评估他们的经历。我们将通过焦点小组进一步考虑转诊医生和患者的意见。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是确定返回哪些结果，而且还确定如何最好地将这些基因组数据纳入医疗记录中。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；这种新基因的发现可以影响预防和治疗。