Investigation Of Discordant Sibling Pairs From Hereditary Breast Cancer (Hbc) Families

1538Background: Women who undergo testing for hereditary breast cancer (HBC) may be offered a panel of up to 40 genes but the majority of women tested have no mutation identified on these panels. This implies the existence of additional genes associated with HBC. Using a family-based design, our goal is to identify novel gene(s) or variants associated with HBC. Methods: We enrolled discordant sister pairs (one with and one without breast cancer) from families with ≥3 breast cancers (one diagnosed ≤50) on an IRB approved study. Germline DNA was extracted and whole exome sequencing performed. In order to highlight variants identified by our sequencing analysis as putative risk alleles, we used publicly available bioinformatics tools and genomic databases. By combining information across these resources, we generated a list of candidate risk alleles. Discordant allele scores were calculated for each of the variants (from genes with known cancer associations, and variants likely to alter function) seen in ≥1 ...