BRCA Exchange addresses ‘urgent need’ for data sharing in cancer predisposition research
The Global Alliance for Genomics and Health has launched a global public repository that includes data on thousands of inherited variants in the BRCA1 and BRCA2 genes.
The BRCA Exchange — funded in part by NCI and through the Cancer Moonshot — is a long-term demonstration project that allows clinicians to review expert classifications of BRCA1 and BRCA2 variants as part of their individual assessment of complex questions related to cancer prevention, screening and intervention for high-risk patients.
The repository — created through the 5-year BRCA Challenge project — is accessible via a website, www.brcaexchange.org, and smartphone app.
“This project has yielded a meta-analysis of BRCA1 and BRCA2 variants collected from multiple sources to understand how experts annotate specific mutations in the two genes,” Stephen J. Chanock, MD, director of the division of cancer epidemiology and genetics of NCI, said in a press release. “There is 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.”
HemOnc Today spoke with Chanock about how this effort came about, how the exchange works and the need for such a repository.
Question: How did this effort come about?
Answer: Approximately 5 years ago, the BRCA Challenge was proposed at the second meeting of the Global Alliance for Genomics and Health. The consensus was that Professor Sir John Burn of Newcastle University in the United Kingdom and I lead this important driver project for the alliance. The project was designed to accelerate the aggregation of data on inherited mutations in BRCA1 and BRCA2 to generate an informed understanding of the impact of variation in these genes on cancer risk. Variant information has been drawn from clinical as well as population databases, including Breast Cancer Information Core, ClinVar and Leiden Open Variation Database. A key issue has been the expert classification by the international consortium, known as the Evidence-based Network for the Interpretation of Germline Mutant Alleles, or ENIGMA.
Q: How does it work?
A: The BRCA Challenge goals are to share BRCA1 and BRCA2 data publicly; create an environment for collaborative variant curation with access to evidence, such as phenotypes, family history, genetic data and functional studies; create a curated list of BRCA variants, interpreted by expert consensus, to enable — without dictating — accurate clinical care; address the social, ethical and legal challenges to global data sharing; and engage with patient advocacy organizations from around the world. The BRCA Exchange displays more than 21,000 unique variants. More than 7,000 are displayed with expert classifications by ENIGMA, of which approximately 3,700 have been deemed pathogenic. The data can be accessed online through the website, or on the free app, BRCA Exchange, available on Google Play or the App Store.
Q: What is the need for something like this?
A: Inherited variations in BRCA1 and BRCA2 can indicate genetic predisposition to breast, ovarian and other cancers, but a large proportion of observed variants are not disease-associated. This represents a ‘big data’ resource that enables clinicians and patients to review expert classification of variants in these major cancer predisposition genes.
Q: What are the next steps?
A: Ongoing work includes outreach to national centers with diagnostic data to encourage even more data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variations in BRCA1 and BRCA2. Our understanding will improve further as additional information about each variant continues to accumulate.
Q: Is there anything else that you would like to mention?
A: The BRCA Challenge provides proof-of-principle for similar investigations of other high-risk cancer predisposition genes, such as TP53, CDKN2A, PTEN and others. – by Jennifer Southall
For more information:
Stephen J. Chanock, MD, can be reached at National Cancer Institute, Division of Cancer Epidemiology and Genetics, NCI Shady Grove, Room 7E412, Rockville, MD 20850; email: firstname.lastname@example.org.
Disclosure: Chanock reports no relevant financial disclosures.