UC Santa Cruz Genomics Institute helps develop BRCA Exchange to inform understanding of cancer risk by aggregating data on thousands of BRCA1 and BRCA2 variants

UC Santa Cruz Genomics Institute helps develop BRCA Exchange to inform understanding of cancer risk by aggregating data on thousands of BRCA1 and BRCA2 variants

SANTA CRUZ, CA – January 8, 2019 Researchers at the UC Santa Cruz Genomics Institute have helped develop a global resource that includes data on thousands of inherited variants in the BRCA1 and BRCA2 genes. The BRCA Exchange was created through the BRCA Challenge, a long-term demonstration project initiated by the Global Alliance for Genomics and Health (GA4GH) to enhance sharing of BRCA1/BRCA2 data. The resource, available through a website and a new smartphone app, allows clinicians to review expert classifications of variants in these major cancer predisposition genes as part of their individual assessment of complex questions related to cancer prevention, screening, and intervention for high-risk patients.

A paper detailing the development of the BRCA Exchange was published January 8, 2019 by PLOS Genetics.

“Sharing genetic data is very challenging, due to a number of regulatory, legal and ethical restrictions, explained researcher and BRCA Exchange project lead Melissa Cline, Ph.D.  “At the same time, it is necessary because “rare” genetic variants are actually collectively common,” Cline continued.

In fact, one recent study (Karczewski, The ExAC browser, Nucleic Acids 2017) showed that the average human exome carries upwards of seven highly rare genetic variants.  Many of these variants will be inconsequential, but a few will fall into clinically important genes such as BRCA1, and no single institution will gather enough data on these variants for robust clinical interpretation.  

Recognizing this, the Global Alliance for Genomics and Health (GA4GH) launched a project called BRCA Challenge, to bring together leading experts to address these challenges for BRCA1 and 2 as a model for other genes.  The BRCA team produced a web site, brcaexchange.org and smartphone app, which aggregate all available information on BRCA1 and 2 variants with the goal of fostering greater variant interpretation, and to serve as a model for additional genes.

The consortium brings together some of the world’s leading scientists, science policy scholars, legal scholars and others, all working  together (mostly volunteering their time) towards a vision of better data sharing. The five-year BRCA Challenge project was funded in part by the National Cancer Institute (NCI), part of the National Institutes of Health, and through the Cancer Moonshot.

“This project has yielded a meta-analysis of BRCA1 and BRCA2 variants collected from multiple sources to understand how experts annotate specific variants in the two genes,” said Stephen J. Chanock, M.D., director of NCI’s Division of Cancer Epidemiology and Genetics and 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 and data sharing can be achieved and can provide the latest and best quality information to enable clinicians and individuals to improve care.”

Certain inherited variants in BRCA1 and BRCA2 can increase the risk of breast, ovarian, and other cancers by varying degrees, whereas other variants are not associated with disease. Clinicians and patients need to know whether a given variant is likely to be disease-associated (pathogenic) and how likely a pathogenic variant is to cause cancer (penetrance). Until now, the available data on the inherited variants in these genes was not aggregated in a comprehensive way.

The BRCA Exchange dataset comprises information from existing clinical databases—Breast Cancer Information Core, ClinVar, and the Leiden Open Variation Database—as well as population databases and data from clinicians, clinical laboratories, and researchers worldwide. It currently includes more than 20,000 unique BRCA1 and BRCA2 variants. More than 7,200 variants in the database have been classified by an expert panel, the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), and approximately 4,800  of these variants are known to cause disease. The BRCA Exchange pools variants from data resources worldwide, which should lead to inclusion of rare variants that are very occasionally observed.

With a single-point-of-access website (www.brcaexchange.org), the BRCA Exchange provides information on these gene variants to clinicians, researchers, data scientists, patients, and patient advocates. It also serves as a demonstration project showing that this kind of comprehensive data sharing—requiring collaboration across hundreds of organizations, the establishment of an infrastructure to house the information, and the development of data-sharing protocols—is possible for other cancer predisposition genes and, indeed, for genes associated with other diseases.

Next steps for the project include collaboration with additional global data generators and data holders, continued technical development, and increased engagement with patients and patient advocates around the world.

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About the UC Santa Cruz Genomics Institute

Comprising diverse researchers from a variety of disciplines across academic divisions, the UC Santa Cruz Genomics Institute leads UC Santa Cruz’s efforts to unlock the world’s genomic data and accelerate breakthroughs in health and evolutionary biology. Our platforms, technologies, and scientists unite global communities to create and deploy data-driven, life-saving treatments and innovative environmental and conservation efforts.

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Home to the UC Santa Cruz Genomics Institute, the Baskin School of Engineering at UC Santa Cruz offers unique opportunities for education, research and training. Faculty and students seek new approaches to critical 21st century challenges within the domains of data science, genomics, bioinformatics, biotechnology, statistical modeling, high performance computing, sustainability engineering, human-centered design, communications, optoelectronics and photonics, networking and technology management. By leveraging novel tools that emerge from changing technologies, we have pioneered new engineering approaches and disciplines, examples of which include biomolecular engineering, computational media, and technology and information management.

About the BRCA Exchange

The UC Santa Cruz Genomics Institute co-founded the BRCA Exchange, a global open source resource governed by the Global Alliance for Genomics and Health (GA4GH). This network hosts clinical breast-cancer data contributed by geneticists from several countries, and has become the world’s largest public, open repository of information on BRCA1 and BRCA2 genetic variations and their implications for cancer risk. Watch this video to learn more about BRCA Exchange, and check out Setting The Standard: The Path For International Data Sharing and BRCA Exchange: Data Sharing for the Benefit of Science and Medicine for in-depth, first-person stories.