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: 9117004
• 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/9117004
• 关键词: Base Pairing; Bioethics; CLIA certified; 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; genomic data; human DNA; individualized prevention; multidisciplinary; novel; personalized medicine; 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期望。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。同时，DNA测序技术的进步提高了通量并降低了成本。我们现在可以广泛利用我们对人类遗传变异的了解，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”的翻译需要多学科的研究。华盛顿大学是临床医学的领导者。 遗传学（班尼特、伯克、拜尔斯、久间和贾维克、莫图尔斯基、拉斯金德和西伯特）、生物伦理学（伯克、贾维克、富勒顿和特立尼达）、第二代测序、变异识别和注释（里德尔和尼克森）、疾病基因发现（布朗宁、希格宁、贾维克、尼克森和里德尔）、医学信息学（塔奇-霍诺奇）和卫生服务研究（希格宁、帕特里克、雷杰和文斯特拉）。在这个高度集成的建议，我们联合收割机这些优势，调查临床使用外显子组数据的方面。我们提出了一项随机对照试验，在华盛顿大学医学遗传学诊所的患者中进行常规治疗与增加外显子组分析，这些患者有结直肠癌/息肉病（CRCP）基因检测的临床指征。我们将评估该技术用于识别临床相关CRCP基因突变、成本和患者衍生措施的有效性。经过专家的审议，以确定应返回的偶然发现的变体，我们也将返回CLIA认证的结果给参与者。我们将获得结构化 来自RCT的常规护理和外显子组的受试者的反馈，以评估他们的经历。我们将进一步考虑使用焦点小组的转介医生和患者的输入。我们将调查需要返回CLIA认证的研究结果的法律的依据。我们工作的一个重要组成部分是不仅要确定返回哪些结果，还要确定如何最好地将这些基因组数据纳入医疗记录。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;这种新的基因发现可以影响预防和治疗。

项目成果

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation and Retrieval.

药物基因组学证据评估智能支持的基于知识的系统：本体驱动的证据表示和检索。

• 发表时间: 2017
• 期刊: AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science
• 作者: Lee,Chia-Ju;Devine,Beth;Tarczy-Hornoch,Peter
• 通讯作者: Tarczy-Hornoch,Peter

Family Studies for Classification of Variants of Uncertain Classification: Current Laboratory Clinical Practice and a New Web-Based Educational Tool.

• DOI: 10.1007/s10897-016-9993-2
• 发表时间: 2016-12
• 期刊: JOURNAL OF GENETIC COUNSELING
• 影响因子: 1.9
• 作者: Garrett, Lauren T.;Hickman, Nathan;Jacobson, Angela;Bennett, Robin L.;Amendola, Laura M.;Rosenthal, Elisabeth A.;Shirts, Brian H.
• 通讯作者: Shirts, Brian H.