Genomic Expert Curation Panels for Pediatric Malignancies

儿科恶性肿瘤基因组专家管理小组

• 批准号: 10413420
• 负责人: Malachi Griffith
• 金额: $ 31.88万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10413420
• 关键词: ABL1 gene; Address; Adopted; Affect; Alleles; American Society of Clinical Oncology; Area; B-Cell Acute Lymphoblastic Leukemia; Benign; Birth; Cancer Etiology; Catalogs; Child; Childhood; ClinVar; Clinical; Clinical assessments; Collaborations; DNA Sequence Alteration; Data; Databases; Development; Diagnosis; Disease; Environment; Event; Funding; Genes; Genetic; Genetic Databases; Genome; Genomics; Goals; Grant; Guidelines; Human Genetics; Informatics; Inherited; Institutes; Knowledge; Laboratories; Link; Los Angeles; Lymphoblastic Leukemia; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Molecular; Molecular Profiling; Mutation; National Institute of Child Health and Human Development; Pathway interactions; Pediatric Hospitals; Pediatric Neoplasm; Phenotype; Philadelphia; Policies; Population; Prediction of Response to Therapy; Procedures; Process; Professional Organizations; Prognosis; Publications; Registries; Reproducibility; Research Personnel; Resources; Somatic Mutation; Testing; Time; Translating; United States National Institutes of Health; Universities; Variant; Washington; accurate diagnosis; actionable mutation; adjudicate; anticancer research; cancer diagnosis; clinical application; clinical decision-making; clinically actionable; clinically relevant; clinically significant; crowdsourcing; data curation; data exchange; data hub; data standards; experience; genetic counselor; genetic variant; genome-wide; genomic data; information display; knowledgebase; novel; novel strategies; precision oncology; repository; response; treatment response; tumor; user-friendly; working group; young adult

Project Summary/Abstract The goal of this proposal is to develop expert panels focused on curating evidence for the clinical application of somatic mutations associated with childhood cancers. Tumors in the pediatric population have unique genetic profiles that can affect their diagnosis, prognosis and treatment. There is currently a gap in representation of somatic variants for childhood tumors in public cancer databases and knowledgebases. New approaches for evidence curation are needed to identify important mutations in childhood cancers for both diagnosis and therapy response. To address these gaps, our application builds on two prominent developments in the field led by our team. First, as the ClinGen Somatic Clinical Domain Working Group (CDWG) we developed the Minimal Variant Level Data (MVLD) standard to promote sharing and use of gene variants in precision oncology. Second, we developed the Clinical Interpretation of Variants in Cancer (CIViC) expert crowdsourced platform for somatic curation and clinical interpretation. Our goals are to: (1) systematically catalog the clinical relevance of common, rare, and novel variants identified through gene-specific and genome-scale testing in childhood cancers; (2) partner with ClinGen, ClinVar, guideline-setting professional organizations, and other relevant global efforts to translate and present the knowledge derived from genome researchers and clinical laboratories; and (3) develop informatics support for variant assessment of clinical actionability, information display, interfacing with relevant databases, and dissemination. To accomplish these goals we developed a collaboration over the past three years through the ClinGen Somatic CDWG among researchers at Washington University, Georgetown University, and Children’s Hospital Los Angeles that includes clinical and molecular geneticists, genetic counselors, bioinformaticians, and genomic database experts to advance the use of genomic data in childhood cancers. Specifically, we will establish pilot variant curation expert panels (VCEPs) to assess clinical relevance and actionability of somatic variants in pediatric cancers. Our initial focus will be on two disease areas, with timely relevance, pediatric malignancies with NTRK fusions and BCR-ABL1 (Philadelphia)-like B-lymphoblastic leukemia (Ph-like B-ALL). We will adopt ClinGen’s existing VCEP policies and processes for assessing variants of strong clinical significance, potential clinical significance, unknown clinical significance, and benign or likely benign variants in childhood cancers. We will adapt and enhance the CIViC platform to support these expert panels. The CIViC platform will also provide the curated evidence in standard formats for exchange of data with ClinVar and ClinGen resources. Finally, we will seek FDA recognition for the evidence repository developed and curated through this grant.

项目概要/摘要 该提案的目标是建立专家小组，专注于为临床应用提供证据 与儿童癌症相关的体细胞突变。儿科人群的肿瘤具有独特的遗传性 可以影响他们的诊断、预后和治疗的概况。目前代表性存在差距 公共癌症数据库和知识库中儿童肿瘤的体细胞变异。新的 需要采取证据管理方法来识别儿童癌症中的重要突变 诊断和治疗反应。为了解决这些差距，我们的应用程序建立在两个突出的基础上 由我们团队领导的领域的发展。首先，作为 ClinGen 躯体临床领域工作组 (CDWG) 我们制定了最小变异水平数据 (MVLD) 标准，以促进基因的共享和使用 精准肿瘤学的变体。其次，我们开发了癌症变异的临床解释 (CIViC) 用于躯体治疗和临床解释的专家众包平台。我们的目标是：（1） 系统地对通过识别的常见、罕见和新颖变异的临床相关性进行分类 儿童癌症的基因特异性和基因组规模测试； (2) 与 ClinGen、ClinVar 合作， 制定指南的专业组织，以及翻译和呈现指南的其他相关全球努力 来自基因组研究人员和临床实验室的知识； (3) 开发信息学支持 临床可操作性的变量评估、信息显示、与相关数据库的接口，以及 传播。为了实现这些目标，我们在过去三年中通过以下方式开展了合作： 华盛顿大学、乔治城大学和儿童医院的研究人员参加了 ClinGen Somatic CDWG 洛杉矶医院包括临床和分子遗传学家、遗传咨询师、生物信息学家、 和基因组数据库专家共同推进基因组数据在儿童癌症中的应用。具体来说，我们将 建立试点变异管理专家小组（VCEP）来评估体细胞变异的临床相关性和可操作性 儿童癌症的变异。我们最初的重点将放在两个具有及时相关性的疾病领域：儿科 NTRK 融合恶性肿瘤和 BCR-ABL1（费城）样 B 淋巴细胞白血病（Ph 样 B-ALL）。 我们将采用 ClinGen 现有的 VCEP 政策和流程来评估强临床的变体 意义、潜在临床意义、未知临床意义以及良性或可能良性变异 儿童癌症。我们将调整和增强 CIViC 平台来支持这些专家小组。公民社会 平台还将提供标准格式的精选证据，以便与 ClinVar 和 临床资源。最后，我们将寻求 FDA 对开发和策划的证据存储库的认可 通过这笔赠款。