Hereditary Breast Cancer
The research in the Nathanson Group in hereditary breast and ovarian cancer started when I was post-doctoral fellow, training under Dr. Barbara Weber. Most recently, we have published studies demonstrating variable risks of breast and ovarian cancers with differing mutation types and locations with BRCA1 and BRCA2 (JAMA, 2015), and described the world-wide distribution of mutations (Hum Mutat, 2018). My group has evaluated the rate of moderate risk gene mutations in early onset breast cancer (Genet Med, 2015; NPJ Breast Cancer ,2017), contributed to consensus statements on the risk of these mutations (NEJM, 2015; Nat Rev Clinic Oncol, 2016), and evaluated the use of the ACMG guidelines for variant annotation of these genes (Am J Hum Genet, 2016). We published a somatic characterization of tumors associated with BRCA1/2 germline mutations and demonstrated that a significant proportion do not have allele-specific loss of heterozygosity, associated with differential genetic/genomic characteristics and survival after treatment (Nat Comm, 2017). We have preliminary data following up.
- Identification of novel breast cancer susceptibility genes using large scale sequencing in high risk and case-control cohort studies
- Characterization of moderate penetrance breast cancer susceptibility genes in large cohorts
- Characterization of immunogenicity in BRCA1/2 mutation associated cancers, understanding the associated molecular features and role of aneuploidy (working with cancer immunologists at Penn Medicine)
- Understanding tumor heterogeneity in BRCA1/2 mutation associated cancers, by using single cell sequencing, high-depth targeted sequencing and large scale
- Working with Dr. E. John Wherry’s group to elucidate immune function in healthy BRCA1/2 mutation carriers