Pre-cancer Microenvironment in Fallopian Tubes from BRCA1 Mutation Carriers

Germline BRCA1 mutations have been associated with increased risk of high-grade serous ovarian cancer as well as early onset of cancerous transformation in the fallopian tube. BRCA1 mutations have also been associated with accelerated reproductive aging and premature infertility due to reduced oocyte reserve. In mouse models, the loss of BRCA1 function resulted in brain development and heart regeneration defects, suggesting that BRCA1 heterozygosity may be associated with a systemic defect in tissue maintenance. We hypothesize that normal fallopian tubes from BRCA1 mutation carriers have unique molecular and histomorphometric features that underlie the early onset of cancerous transformation. Our goal is to integrate multidimensional image analysis, RNA sequencing, and clinical and demographic data to identify specific features that may generate a pre-cancer microenvironment in BRCA1 mutation carriers.