Yael Raz Yana, MD
Cedars-Sinai Medical Center
2019 Cookie Laughlin Scholar Award
Studying the Fallopian Tubes of BRCA Mutation Carriers to Understand the Infrastructure for Malignant Transformation
Though the majority of ovarian cancer patients are postmenopausal, it is unknown how age and postmenopausal conditions contribute to cancer development. Women with inherited BRCA1 gene mutations are at increased risk of ovarian cancer. It is now accepted that most ovarian cancers originate in the fallopian tube. Dr. Raz Yana will study how postmenopausal conditions and status of BRCA mutation alter fallopian tubes to promote ovarian cancer. Fallopian tubes contain several types of cells, including secretory cells and ciliated cells. Dr. Raz Yana and colleagues observed secretory and ciliated cells often form large clusters in fallopian tubes from postmenopausal women. The ratios of secretory and ciliated cells are different in clusters in fallopian tubes of women with BRCA1 mutations compared to women of the same age without BRCA1 mutation. Importantly, secretory cell ‘runs’ have been associated with increased risk of ovarian cancer, suggesting that secretory cell clusters may represent a potential pre-cancer environment. Dr. Raz Yana hypothesizes that fallopian tubes from women with BRCA mutations have earlier and more frequent cell clustering compared to women without BRCA mutation, which in turn creates a more permissive microenvironment for the initiation and progression of cancer. Dr. Raz Yana and colleagues will examine abnormal cell clustering in the fallopian tube tissues of healthy women with BRCA mutations and identify which changes in expression of genes potentially contribute to the formation of the pre-cancer environment. This may lead to the development of new strategies for ovarian cancer prevention and detection.