title: Patient-derived ovarian tumor xenografts recapitulate human clinicopathology and genetic alterations.
abstract: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. On the basis of its histopathology and molecular-genomic changes, ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC xenografts that recapitulate the molecular and biologic heterogeneity of human ovarian cancer. Thirty-four EOC xenografts were successfully established, either subcutaneously or intraperitoneally, in nude mice. The xenografts were histologically similar to the corresponding patient tumor and comprised all the major ovarian cancer subtypes. After orthotopic transplantation in the bursa of the mouse ovary, they disseminate into the organs of the peritoneal cavity and produce ascites, typical of ovarian cancer. Gene expression analysis and mutation status indicated a high degree of similarity with the original patient and discriminate different subsets of xenografts. They were very responsive, responsive, and resistant to cisplatin, resembling the clinical situation in ovarian cancer. This panel of patient-derived EOC xenografts that recapitulate the recently type I and type II classification serves to study the biology of ovarian cancer, identify tumor-specific molecular markers, and develop novel treatment modalities.
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bizzaro
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cesca
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Guffanti
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Decio
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ghilardi
authors.affiliation: Department of Pathology, San Gerardo Hospital, Monza, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Perego
authors.affiliation: Obstetrics and Gynecology Clinic, San Gerardo Hospital, Monza, Italy.
authors.forename: Robert
authors.initials: R
authors.lastname: Fruscio
authors.affiliation: Obstetrics and Gynecology Clinic, San Gerardo Hospital, Monza, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Buda
authors.affiliation: Obstetrics and Gynecology Clinic, San Gerardo Hospital, Monza, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Milani
authors.affiliation: Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia Valenta, Biella, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ostano
authors.affiliation: Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia Valenta, Biella, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chiorino
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Bani
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. giovanna.damia@marionegri.it raffaella.giavazzi@marionegri.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Damia
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. giovanna.damia@marionegri.it raffaella.giavazzi@marionegri.it.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giavazzi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000379:methods*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin