IS OVARIAN CANCER A MISNOMER? EXPLORING OVARIAN CANCER ORIGINS IN THE MOUSE

摘要

Ovarian cancer is a generic term that encompasses several different tumor types. The most common and lethal type is known as high-grade serous carcinoma. The cellular origin of high-grade serous carcinoma has been debated for many years, but recent studies suggest that many, if not most, arise from epithelium in the fallopian tube rather than from the ovarian surface epithelium. Genetically engineered mice have been used to study the consequences of transforming epithelium in the oviduct (mouse fallopian tube equivalent) versus the ovarian surface epithelium, and to test whether genetic alterations characteristic of specific types of human ovarian cancers will lead to morphologically and biologically similar tumors in the mouse. Recent studies show that the mouse tumor phenotype is highly dependent on both cell of origin and the specific genetic alterations underlying neoplastic transformation, with mouse tumors based on transformation of oviductal epithelium more closely recapitulating their human tumor counterparts than those based on ovarian surface epithelium transformation. Understanding the cellular origins of ovarian cancer has significant implications for improving ovarian cancer prevention and early detection.