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、符合 CLIA 标准的基因组测试和尖端研究—— 对 PEU 参与的 MM、CRC 和 CHOL 患者进行水平分析。此次测试将 这三项研究均对来自 300 名患者的诊断性肿瘤样本和匹配的正常组织进行了研究 WU PE-CGS 研究项目期间的癌症类型。来自其中 150 个的额外后续样本 还将在疾病进展期间对患者进行分析。 GCU 的样品处理将包括核酸 酸提取和质量控制。将使用 250X 肿瘤/正常外显子组测序分析诊断样本 (WES) 对基因水平单核苷酸变异（SNV 和 插入/删除（indel）。将进行仅肿瘤全基因组测序（60X）以检测肿瘤相关结构 突变和肿瘤 RNA-seq 将支持、确认和扩展基于 DNA 的检测结果。瘤 组织和/或游离 DNA 也将使用独特的靶向深度测序（>10,000X）进行分析 分子指数（UMI）用于灵敏检测和监测肿瘤相关突变。所有这些 检测将使用符合 CLIA 的程序和综合质量管理实践进行。这 GCU 还将对选定的样本进行研究级 scRNA-Seq、蛋白质组学和细胞成像研究 样本以增强我们对这些肿瘤类型的了解。基因组检测将按照 诊断样本和后续采集的逐年组合的计划时间表，其中少量 被选中进行研究的候选人数量。这些检测的结果将返回给参与者 使用取决于参与者偏好的分层报告系统。一级结果将突出显示发现 具有从个体参与者的 CLIA 测序中获得的已确定的临床相关性，包括 致病性、肿瘤相关的体细胞驱动因素和遗传突变，根据临床可采取行动 已发布的指南，并将使用已建立的躯体驱动程序分类进行报告 致病性种系变异、其临床意义和可能的作用。参与者还可以选择 接收第 2 层结果，该结果将包含来自相同 CLIA 兼容数据的附加突变 通过先进的方法进行识别，并通过功能注释预测具有临床相关性，如 以及用于监测肿瘤随时间演变的后续样本的靶向测序结果。 研究级第 3 级分子研究也可以作为汇总、去识别化的报告提供给参与者 可用于增强和扩展对其个性化 CLIA 结果的解释。这些结果将 也可以安全上传到 NCI 基因组数据共享 (GDC)，供癌症生物学使用 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 整个 WU PE-CGS 项目。