Brca1 Circos: A Visualization Tool For Brca1 Missense Variants

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Germline mutations in BRCA1 have been associated with a significantly increased risk of developing breast and ovarian cancers. A large number of variants have been identified in BRCA1 and are reported as pathogenic, non-pathogenic, or as variants of uncertain significance (VUS). Test results reporting pathogenic or non-pathogenic variants can be used by physicians and genetic counselors to help patients in making important clinical decisions. Around 10-15% of the reported BRCA1 and BRCA2 variants are clearly pathogenic and 5% of these reported variants are VUS. Results reporting a VUS can cause anxiety and make it difficult to advise the patient on further clinical intervention to reduce their risk of developing the disease. Many of these VUSs are non-synonymous single amino acid changes leading to missense changes. A number of previous studies have focused on assessing the functional impact of these changes on the BRCA1 protein. BRCA1 is a gene product with pleiotropic functions and therefore, different functional assays are used in these studies to analyze the variant's impact on function. However, information on the functional impact of VUS is currently not consolidated and collecting available information on missense variants depends on multiple database searches and literature review. Moreover, methods to incorporate functional data into multifactorial models have recently been developed highlighting the need for a common resource to facilitate analysis. Realizing the need for a resource that facilitates the global visualization and analysis of these variants we have developed a visualization tool for multidimensional data using Circos (http://circos.ca) to aggregate the data from all published studies that have assessed these missense variants. Circos plots have been used in the literature to represent genomic data and we have used the same concept to illustrate variants in BRCA1. We have included ∼700 variants for which we have 30 different functional experiments from various studies assessing over 150 missense variants. Results are color coded to uniformly depict various degrees of functional impact on the BRCA1 protein function so that information for any variant can be obtained in a snapshot without having to perform extensive literature searches. Therefore, we believe clinical geneticists and genetic counselors can use this research tool as a quick reference to analyze all the missense variants that have been identified along with associated information to characterize them when faced with the challenge of advising a patient with these types of VUSs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4444. doi:1538-7445.AM2012-4444