domingo, 6 de enero de 2019

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2. - PubMed - NCBI

2018 Dec 26;14(12):e1007752. doi: 10.1371/journal.pgen.1007752. [Epub ahead of print]

BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

Cline MS1, Liao RG2, Parsons MT3, Paten B4, Alquaddoomi F5,6,7, Antoniou A8, Baxter S4, Brody L9, Cook-Deegan R10, Coffin A1, Couch FJ11, Craft B1, Currie R1, Dlott CC1, Dolman L12, den Dunnen JT13, Dyke SOM14, Domchek SM15, Easton D8, Fischmann Z1, Foulkes WD16, Garber J17, Goldgar D18, Goldman MJ1, Goodhand P12, Harrison S19, Haussler D1,4, Kato K20, Knoppers B21, Markello C1,4,22, Nussbaum R23, Offit K24, Plon SE25,26, Rashbass J27, Rehm HL28,29, Robson M24, Rubinstein WS30, Stoppa-Lyonnet D31, Tavtigian S19,32, Thorogood A12,33, Zhang C34, Zimmermann M5,6; BRCA Challenge Authors, Burn J35, Chanock S36, Rätsch G5,6,37,38, Spurdle AB39.

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Abstract

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, www.brcaexchange.org. The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project's outset, of which approximately 6,150 have expert classifications. The data set is based on shared information from existing clinical databases-Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)-as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage 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 variation in BRCA1 and BRCA2.