Transformation of the Fallopian Tube Secretory Epithelium Leads to High-Grade Serous Ovarian Cancer in Brca;Tp53;Pten Models

• DOI: 10.1016/j.ccr.2013.10.013
• Publication Date: 2013-12-09T15:33:44Z
• Authors: Ruth Perets; Gregory A. Wyant; Katherine W. Muto; Jonathan G. Bijron; Barish B. Poole; Kenneth T. Chin; Jin Yun H. Chen; Anders W. Ohman; Corey D. Stepule; Soongu Kwak; Alison M. Karst; Michelle S. Hirsch; Sunita R. Setlur; Christopher P. Crum; Daniela M. Dinulescu; Ronny Drapkin
• Keywords: Ovarian Neoplasms; Cancer Research; Integrases; Genes, BRCA2; Genes, BRCA1; PTEN Phosphohydrolase; Cell Biology; Genes, p53; Epithelium; Cystadenocarcinoma, Serous; 3. Good health; Mice, Inbred C57BL; Mice; PAX8 Transcription Factor; Cell Transformation, Neoplastic; Oncology; Animals; Fallopian Tube Neoplasms; Paired Box Transcription Factors; Female; Neoplasm Grading; Precancerous Conditions

High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Our study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and also establishes serous tubal intraepithelial carcinoma as the precursor lesion to high-grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes. These findings offer an avenue to address clinically important questions that are critical for cancer prevention and early detection in women carrying BRCA1 and BRCA2 mutations.