权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Eliminating variants of uncertain significance in BRCA1, BRCA2 and beyond

消除 BRCA1、BRCA2 及其他中不确定意义的变异

基本信息

批准号：
10005219
负责人：
Melissa Suzanne Cline
金额：
$ 36.88万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10005219
关键词：
Address Anxiety BRCA1 gene BRCA2 gene Bayesian Method Benign Bilateral Biological Assay Cancer Patient Cancer-Predisposing Gene ClinVar Clinical Code Collaborations Colorectal Cancer Communities Credentialing Data Data Analyses Data Collection Epidemiology Family Cancer History Genes Genomic Segment Healthcare Heritability Individual Knowledge Lead Level of Evidence MLH1 gene MSH2 gene MSH6 gene Malignant Neoplasms Malignant neoplasm of ovary Mastectomy Measures Methods Mismatch Repair Modernization PMS2 gene Pathogenicity Patients Penetrance Records Reporting Research Scientist Secure Technology Testing Variant Visualization cancer genetics cancer risk crowdsourcing data integration data sharing data visualization effectiveness testing experimental study gene repair genetic testing genetic variant malignant breast neoplasm novel rare variant repository variant of unknown significance web platform

项目摘要

Abstract By current evidence, roughly one-third of all cancers are driven in part by germline variation. Genetic testing now enables individuals and their doctors to better understand and manage their genetic cancer risk. However, the effectiveness of these tests is limited by the many gaps in our knowledge about the clinical impact of individual variants. Even in the well-studiedBRCA1 and BRCA2 genes, 7280 of the 17156 variants currently in ClinVar are listed as “Variants of Uncertain Significance” (VUS). VUS test reports leave patients with anxiety, and often lead to clinical mismanagement: many doctors frequently recommend bilateral mastectomies for patients with uncertain variants, even though many of those variants will turn out to be benign. Genetic testing will not reach its potential while VUS test reports are still frequent, yet with global data sharing, novel functional screens, and integrative data analysis methods, we can envisage eliminating the VUS problem. We will produce methods for secure data sharing, and integrative analysis that leverages highly predictive modern functional assays. We will demonstrate these approaches on BRCA1 and BRCA2, while outlining their application to other high-penetrance cancer susceptibility genes. We will develop APIs to integrate this new knowledge into the ClinGen and CIViC repositories, to benefit the larger research community. Finally, we will extend the integrative data visualization of BRCA Exchange to additional genes implicated in breast, ovarian and colorectal cancers, which will ultimately benefit tens of thousands of cancer patients and previvors.

摘要