A Transplantable Syngeneic Allograft Mouse Model for Nongestational Choriocarcinoma of the Ovary

Abstract

Nongestational choriocarcinoma is a rare malignancy in humans with poor prognosis. Naturally occurring choriocarcinoma is also rare in laboratory mice, and no genetic mouse model accurately recapitulates the features of this cancer. Here we report development of a genetically engineered mouse (GEM) model with alterations in Brca2, Trp53, and RB that develops ovarian tumors. Most of the ovarian tumors displayed histological characteristics of nongestational choriocarcinoma of the ovary (NGCO) (47%) with abundant syncytiotrophoblasts and cytotrophoblasts, positive immunolabeling for human chorionic gonadotropin, and positive periodic acid–Schiff reaction. The rest of the ovarian tumors were serous epithelial ovarian carcinoma (SEOC) (26%) or mixed tumors consisting of NGCO and SEOC (26%). We further established syngeneic orthotopic mouse models for NGCO by in vivo passaging of GEM tumors. These metastatic models provide a platform for evaluating new treatment strategies in preclinical studies aimed at improving outcomes in choriocarcinoma patients.

Non-Gestational Ovarian Choriocarcinoma: A Rare Ovarian Cancer Subtype

“…One study compared the genetic molecular biology of GOC and NGOC, and found mutations involving DNAJB9, a negative feedback regulator of p53 and NGOC cells showing aberrant expression of p53 [18]. Genetically engineered mouse models with alterations in Trp53 gene were also shown to develop NGOC [19]. NGOC cells have also demonstrated copy number variations and significant amplification of Her2, IKZF3, PGAP3, and C-Myc, which are not demonstrated by GOC; these genes have been implicated in the poorer immunogenicity of NGOC, thus resulting in less sensitivity to chemotherapy [12].…”