Genome Characterization Unit

基因组表征单位

• 批准号: 10294015
• 负责人: Li Ding
• 金额: $ 224.23万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10294015
• 关键词: Address; African American; Biocompatible Materials; Biological Assay; CLIA certified; CLIA certified sequencing; Cancer Biology; Cholangiocarcinoma; Clinical; Clinical Data; Clinical Research; Collection; Colorectal Cancer; Communities; Computers; DNA; Data; Data Commons; Data Storage and Retrieval; Databases; Detection; Diagnostic; Disease Progression; Ensure; Equilibrium; Event; Evolution; Gene Fusion; Genes; Genome; Genomic Data Commons; Genomics; Goals; Guidelines; Health Insurance Portability and Accountability Act; Human Resources; Incidence; Individual; Industry Standard; Inherited; Institutes; Libraries; Malignant Neoplasms; Methodology; Methods; Molecular; Monitor; Multiple Myeloma; Mutation; Normal tissue morphology; Nucleic Acids; Participant; Pathogenicity; Pathologist; Patients; Peptides; Physicians; Practice Management; Preparation; Procedures; Process; Prognosis; Proteomics; Published Comment; Publishing; RNA; Recommendation; Reporting; Research; Running; Sampling; Schedule; Secure; Single Nucleotide Polymorphism; Somatic Mutation; Specimen; Structure; Surveys; System; Testing; Time; TimeLine; Tumor Tissue; Universities; Variant; Washington; archive data; archived data; base; bioinformatics tool; cancer genomics; cancer type; cell free DNA; cellular imaging; clinically actionable; clinically relevant; data acquisition; deep sequencing; early onset; exome sequencing; follow-up; genomic data; health disparity; imaging study; immunogenic; indexing; insertion/deletion mutation; mortality; patient engagement; preference; programs; prospective; research study; single-cell RNA sequencing; statistics; targeted sequencing; transcriptome sequencing; tumor; tumor-immune system interactions; web portal

Project Summary - Genome Characterization Unit (GCU) The GCU will provide comprehensive, end-to-end CLIA-compliant genomic testing and cutting-edge research- level analysis of patients with MM, CRC, and CHOL who are engaged by the PEU. This testing will be conducted on diagnostic tumor samples and matched normal tissue from 300 patients for each of the three cancer types during the WU PE-CGS research program. Additional follow-up samples from 150 of these patients will also be analyzed during disease progression. Sample processing by the GCU will include nucleic acid extraction and QC. Diagnostic samples will be analyzed using 250X tumor/normal exome sequencing (WES) with both somatic and germline analysis for gene-level single nucleotide variants (SNV and insertion/deletions (indels). Tumor-only WGS (60X) will be performed to detect tumor-associated structural mutations, and tumor RNA-seq will support, confirm, and extend findings from the DNA-based assays. Tumor tissue and/or cell-free DNA will also be analyzed with targeted deep sequencing (>10,000X) using unique molecular indexes (UMI) for sensitive detection and monitoring of tumor-associated mutations. All of these assays will be performed using CLIA-compliant procedures with integrated quality management practices. The GCU will also conduct research-level scRNA-Seq, proteomics, and cellular imaging studies on selected samples to enhance our understanding of these tumor types. Genomic assays will proceed according to a planned schedule for year-by-year combinations of diagnostic specimens and follow-up collections, with small numbers of candidates selected for research studies. Results from these assays will be returned to participants using a tiered reporting system that will depend on participant preference. Tier 1 results will highlight findings with established clinical relevance obtained from CLIA sequencing of individual participants, including pathogenic, tumor-associated somatic drivers and inherited mutations that are clinically actionable according to published guidelines and that will be reported using established categorization for somatic drivers and pathogenic germline variants, their clinical implications, and possible actions. Participants can also elect to receive Tier 2 results, which will be comprised of additional mutations from the same CLIA-compliant data that are identified with advanced methods and are predicted to be clinically relevant via functional annotation, as well as results from targeted sequencing of follow-up samples for monitoring tumor evolution over time. Research-level Tier 3 molecular studies may also be provided to participants as aggregate, deidentified reports that can be used to enhance and extend interpretations of their individualized CLIA results. These results will also be securely uploaded to the NCI Genomic Data Commons (GDC) for use by the cancer biology community. All GCU activities will be coordinated with the PEU and EOU to ensure clarity and consistency across the WU PE-CGS program.

项目摘要 - 基因组表征单元（GCU） GCU将提供全面的，端到端的CLIA符合基因组测试和尖端研究 - PEU参与的MM，CRC和CHOL患者的水平分析。这个测试将是 在诊断性肿瘤样品上进行并匹配了300例患者的正常组织 WU PE-CGS研究计划期间的癌症类型。其中150个的其他后续样本 在疾病进展过程中，还将分析患者。 GCU样品处理将包括核 酸提取和QC。将使用250倍肿瘤/正常外显子组测序分析诊断样品 （WES）具有基因级单核苷酸变体的体细胞和种系分析（SNV和 插入/删除（Indels）。将进行仅肿瘤WGS（60倍）以检测与肿瘤相关的结构 突变和肿瘤RNA-seq将支持，确认和扩展基于DNA的测定的发现。瘤 还将使用独特的靶向深度测序（> 10,000x）分析组织和/或无细胞的DNA 分子指数（UMI）用于敏感检测和监测肿瘤相关突变。所有这些 测定将使用符合CLIA兼容的程序进行集成质量管理实践。这 GCU还将对选定 样品以增强我们对这些肿瘤类型的理解。基因组测定将根据 计划的诊断标本和后续收藏的计划时间表 选择用于研究的候选人数量。这些测定的结果将退还给参与者 使用将取决于参与者偏好的分层报告系统。第1层结果将突出显示发现 通过从个人参与者的CLIA测序获得的既定临床相关性，包括 致病性，与肿瘤相关的体细胞驱动器和遗传突变，这些突变在临床上是可起诉的 已发表的指南，将使用既定的躯体驱动器和 致病性种系变体，其临床意义和可能的作用。参与者也可以选择 接收第2层结果，该结果将由来自相同CLIA符合数据的其他突变组成 用高级方法鉴定，并通过功能注释被预测在临床上相关， 以及随着时间的推移靶向测序的靶向测序结果。 研究级别的3个分子研究也可以作为总体报告提供给参与者 可以用来增强和扩展其个性化CLIA结果的解释。这些结果将会 还可以将癌症生物学使用的NCI基因组数据共享（GDC）牢固地上传到 社区。所有GCU活动都将与PEU和EOU协调，以确保清晰度和一致性 在WU PE-CGS计划中。