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: 10708799
• 负责人: Malachi Griffith
• 金额: $ 28.32万
• 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/10708799
• 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; Classification; ClinVar; Clinical; 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; 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; Process Assessment; Professional Organizations; Prognosis; Publications; Registries; Reproducibility; Research Personnel; Resources; Somatic Mutation; Testing; Translating; United States National Institutes of Health; Universities; Variant; Washington; accurate diagnosis; actionable mutation; adjudication; 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.

项目摘要/摘要 该提案的目的是开发专家小组，旨在策划证据，以供临床应用 与儿童癌症相关的体细胞突变。小儿种群中的肿瘤具有独特的遗传 可能影响其诊断，预后和治疗的特征。当前表示存在差距 公共癌症数据库和知识库中儿童肿瘤的躯体变异。新的 需要进行证据策划的方法来识别两者的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 该领域的发展由我们的团队领导。首先，作为克林根躯体临床领域工作组 （CDWG）我们开发了最小的变体水平数据（MVLD）标准，以促进基因共享和使用 精确肿瘤学的变体。其次，我们开发了癌症变异的临床解释（CIVIC） 专家众包躯体策划和临床解释的平台。我们的目标是：（1） 系统地分类通过 儿童癌症中的基因特异性和基因组规模测试； （2）与Clingen，Clinvar合作 指南制定专业组织，以及其他相关的全球努力，以翻译和介绍 源自基因组研究人员和临床实验室的知识； （3）建立信息支持 对临床可行性，信息显示，与相关数据库的接口的变体评估以及 传播。为了实现这些目标，我们在过去三年中开发了合作 华盛顿大学，乔治敦大学研究人员和儿童的Clingen Somatic CDWG 洛杉矶医院，包括临床和分子遗传学家，遗传约会，生物信息学家， 以及基因组数据库专家，以促进儿童癌症中基因组数据的使用。具体来说，我们会的 建立飞行员变体策展专家小组（VCEP），以评估躯体的临床相关性和可行性 小儿取消的变体。我们最初的重点将放在两个疾病领域，及时相关，小儿 NTRK融合和BCR-ABL1（费城）类似B-糖细胞白血病（类似于pH的B-all）的恶性肿瘤。 我们将采用Clingen现有的VCEP政策和流程来评估强大的临床变体 意义，潜在的临床意义，未知的临床意义以及良性或可能的良性变体 童年癌。我们将适应并增强公民平台以支持这些专家小组。公民 平台还将提供标准格式的精选证据，以与Clinvar和Clinvar和 克林根资源。最后，我们将为开发和策划的证据存储库寻求FDA认可。 通过这笔赠款。