Projects

Women who inherit a germline pathogenic mutation of either BRCA1 or BRCA2 suffer an increased risk of breast and ovarian cancer up to ten times that of the normal population. Currently, a woman’s decision to undergo prophylactic mastectomy or oophorectomy is not informed by any specific assessment of eminent cancer risk. A fundamental approach proposed in this project is to provide information regarding the earliest changes that occur in the reproductive epithelium during the transition from normal to pre-malignant stage. Understanding the biology underlying these changes and their relationship to cancer risk might translate into new biomarkers for the detection of imminent cancer development. An approach that combines single cell RNA sequencing with whole genome sequencing might reveal previously unappreciated evidence of instability in the overtly normal reproductive epithelium of women who carry germline mutations of BRCA1 or BRCA2.