Genetic and Epigenetic Effects of BRCA Haploinsufficiency in Fallopian Tube Epithelia

Our long-term goal is to improve cancer prevention and overall prognosis by understanding the etiology and early events driving HGSC. In addition to genomic instability, activation of oncogenes (eg.PI3K, CCNE1 and cMYC),loss of tumor suppressors,(de)differentiation,inflammation,and metabolism all play critical roles in the development and progression of HGSC. Our laboratory and other shave discovered that histologically normal fallopian tube epithelial (FTE) cells with a germline mutation in BRCA1 or BRCA2 have distinct haploinsufficiency transcriptional profiles through ) upregulation of tumor suppressors like C/EBPD and use of non-canonical DNA damage response mechanisms, 2) increase in redox pathways to tolerate oxidative stress and 3) increase in inflammatory cytokines.