DNA repair landscape of discordant sibling pairs from hereditary breast cancer families.

1557 Background: DNA repair plays a significant role in carcinogenesis. The aim of this study is to describe the landscape of germline DNA sequence variation among discordant sister pairs (one with and one without breast cancer) from breast cancer families with an emphasis on DNA repair pathways. Methods: Six sister-pairs were identified from a cohort of high-risk women at University of Vermont Cancer Center. To be eligible for inclusion families must have at least 3 cases of breast cancer, 1 diagnosed under age 50. The unaffected sister must be older than the affected sister’s age at diagnosis. Germline DNA was isolated and full exome sequencing was performed for all 12 women. Computational genomics were utilized to identify putative single nucleotide polymorphisms in DNA repair pathway associated genes. Candidate variants were identified based on the quality of the variant call, distribution among sibling pairs, frequency in the general population, and predicted functional consequences. Results: We obta...