亨茨曼癌症研究所 Helps Develop BRCA Exchange to Inform Underst和ing of Cancer Risk by Aggregating Data on Thous和s of 乳腺癌易感基因1 和 BRCA2 Mutations

亨茨曼癌症研究所（HCI）的研究人员 犹他大学 (U of U) contributed to the development of a global resource that includes data on thous和s of inherited 变体 in the 乳腺癌易感基因1 和 BRCA2 基因. This resource, called the BRCA Exchange, is now available to the 公共. BRCA交流是通过BRCA挑战创建的, a long-term demonstration project initiated by the Global Alliance for Genomics 和 Health (GA4GH) to enhance sharing of 乳腺癌易感基因1和BRCA2 data. The new resource will allow clinicians to review expert classifications of 变体 in these major cancer predisposition 基因 as part of their individual assessment of cancer prevention, 放映, 以及对乳腺癌高风险患者的干预措施, 卵巢, 以及其他一些癌症.

肖恩·塔夫蒂吉安博士, a cancer researcher at HCI 和 professor of oncological sciences 在 U of U, 和大卫·戈德加, 博士学位, also a cancer researcher at HCI 和 adjunct professor in the department of dermatology 在 U of U, have been involved in research on these two 基因 since before they were actually discovered. They’ve also been involved in the evaluation of sequence 变体 observed in the 基因 since shortly after the 基因’ discovery. 他们对研究的贡献增加了历史背景, 关于基因结构的详细知识, 和 knowledge on methods of variant classification to the BRCA Exchange.

"Dr. Goldgar 和 I have been excited to see discoveries we contributed to in the 1990s translated for the benefit of 病人 和 their at-risk relatives,塔夫蒂吉安说. "Yet the problem of classifying sequence 变体 observed during clinical testing has proven difficult. Solutions to this problem will be accelerated by the world-wide data sharing effort the BRCA Exchange is going to enable, 为世界各地的患者带来更大的利益."

The five-year BRCA Challenge project was funded in part by the National Cancer Institute (NCI), 是国家卫生研究院的一部分, 通过 癌症的月球探测器. A paper detailing the development of the BRCA Exchange was published today by 公共科学图书馆遗传学.

“这个项目产生了一项荟萃分析 乳腺癌易感基因1 和 BRCA2 变体 collected from multiple sources to underst和 how experts annotate specific mutations in the two 基因,Stephen J说。. Chanock, MD, director of NCI’s Division of Cancer Epidemiology 和 Genetics 和 lead author of the paper. "There’s an urgent need for sharing data in cancer predisposition research. The BRCA Exchange is proof-of-principle that large-scale collaboration 和 data sharing can be achieved 和 can provide the latest 和 best quality information to enable clinicians 和 individuals to improve care."

Certain inherited 变体 in these 基因 can increase the risk of breast, 卵巢, 以及其他不同程度的癌症, 而其他变异则与疾病无关. Clinicians 和 病人 need to know whether a given variant is likely to be disease-associated (pathogenic) 和 how likely a pathogenic variant is to cause cancer. 直到现在, the available data on the inherited 变体 in these 基因 was not aggregated in a comprehensive way.

The BRCA Exchange dataset comprises information from existing clinical databases—Breast Cancer Information Core, ClinVar, 和 the Leiden Open Variation Database (LOVD)—as well as population databases 和 data from clinicians, 临床实验室, 全世界的研究人员. 它目前包含超过20,000个独特的 乳腺癌易感基因1 和 BRCA2 变体. 6人以上,100 变体 in the database have been classified by an expert panel called the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA). 在这6100种变异中，大约有3700种已知会导致疾病. BRCA Exchange现在汇集了来自世界各地数据资源的变体, which should lead to inclusion of rare 变体 that are very occasionally observed.

与一个 单点访问网站, the BRCA Exchange now provides information on these gene 变体 to clinicians, 研究人员, 数据科学家, 病人, 病人权益倡导者. It also serves as a demonstration project showing that this kind of comprehensive data sharing—requiring collaboration across hundreds of organizations, 建立容纳信息的基础设施, 和 the development of data-sharing protocols—is possible for other cancer predisposition 基因 和, 事实上, 与其他疾病相关的基因.

Next steps for the project include collaboration with additional global data generators 和 data holders, 持续的技术发展, 和 increased engagement with 病人 病人权益倡导者 around the world.

The HCI portion of this research was supported by National Institutes of Health/National Cancer Institute including P30 CA042014 和 the 亨斯迈癌症基金会.