Shared Genomic Segment Analysis and Tumor Subtyping in High-Risk BrCa Pedigrees

Breast cancer (BC) is the most common malignancy in women. In 2014, there were an estimated 3.3 million women living with BC in the United States. Its incidence represents 15% of all new cancer cases, with over 250,000 estimated new cases in 2017, and approximately 12.4% of women will receive a BC diagnosis in their lifetime. It is unquestionably an issue with substantial impact on public health and healthcare. Cancer mortality rates have consistently improved since 1992, but BC is still responsible for over 40,000 deaths per year. The evidence for a genetic component is established and high-risk genes (BRCA1 and BRCA2) and have been mapped and are used clinically for risk management. This study includes 11 high-risk pedigrees (selected as likely not due to BRCA1/2). In the 11 high-risk pedigrees only breast cancer cases were studied: high-density SNP genotypes (OMNIExpress array) were generated on 356 individuals; PAM50 gene expression for 238 tumors, germline whole genome sequencing in 23, and germline targeted panel sequencing (~600 genes) for 200 cases. For high-density genotyping and whole genome sequencing, only one per pedigree is deposited (N=11 and N=3, respectively). Panel sequencing data for an additional 178 non-pedigree cases and controls were also generated. Associated individual-level data include: status (breast cancer), PAM50 subtype, pedigree membership, age and year at diagnosis for breast cancer, age at sampling, sex, race and ethnicity. Full data for the pedigrees and pedigree structure can be acquired under an alternate data sharing plan.