title: Transformation of the fallopian tube secretory epithelium leads to high-grade serous ovarian cancer in Brca;Tp53;Pten models.
abstract: 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.
authors: Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors: Ruth
authors: R
authors: Perets
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Gregory A
authors: GA
authors: Wyant
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Katherine W
authors: KW
authors: Muto
authors: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Jonathan G
authors: JG
authors: Bijron
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Barish B
authors: BB
authors: Poole
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Kenneth T
authors: KT
authors: Chin
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Jin Yun H
authors: JY
authors: Chen
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Anders W
authors: AW
authors: Ohman
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Corey D
authors: CD
authors: Stepule
authors: Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors: Soongu
authors: S
authors: Kwak
authors: Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors: Alison M
authors: AM
authors: Karst
authors: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Michelle S
authors: MS
authors: Hirsch
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Sunita R
authors: SR
authors: Setlur
authors: Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Christopher P
authors: CP
authors: Crum
authors: Eugene Braunwald Research Center, Department of Pathology, Harvard Medical School, Boston, MA 02115, USA; Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ddinulescu@rics.bwh.harvard.edu.
authors: Daniela M
authors: DM
authors: Dinulescu
authors: Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ronny_drapkin@dfci.harvard.edu.
authors: Ronny
authors: R
authors: Drapkin
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D018284:Cystadenocarcinoma, Serous / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000473:pathology*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016158:Genes, p53; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000072636:PAX8 Transcription Factor; D051059:PTEN Phosphohydrolase / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology; D011230:Precancerous Conditions / Q000473:pathology*
chemical_list: D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse