Abstract 1193: Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma

Abstract

Abstract Despite comprising up to 10% of pediatric CNS tumors, an animal model of intracranial germinoma has not been previously established. Standard of case for germinoma is radiation therapy, with recent evidence that neo-adjuvant chemotherapy may allow reduction of radiation dose, but concern for neuro-cognitive toxicity remains despite the reduction of radiation. A clinically relevant animal model of germinoma would facilitate investigation and discovery of novel agents which may obviate the need for radiation in the future. To develop xenograft mouse models, we implanted germinoma tumor cells from two children with metastatic disease, one from a surgical specimen of a cervical metastatic tumor and the second from disseminated tumor cells in the CSF, directly into the right cerebral hemispheres of NOD-SCID mice. Both patient tumor samples have undergone whole exome sequencing; one of the two models has a germinoma-associated mutation in c-kit. The tumors have been serially passaged in xenografts for 3-5 times, with each passaged tumor maintaining the ability to generate tumors, suggestive of the persistence of viable tumorigenic/tumor stem cells. Data from additional tumor models established by our lab have confirmed molecular and genetic fidelity between xenograft-initiating human brain tumors and their corresponding murine models. The orthotopic location in the mouse brain of the xenograft model should also reasonably replicate the human germinoma tumor microenvironment. Cultured cells are currently growing from both tumor models in order to establish germinoma cell lines. In summary, our orthotopic xenograft murine models of two metastatic pediatric germinomas are the first to be established for this tumor type. These models will allow much needed pre-clinical drug testing of chemotherapeutics and combination therapies as well as further biologic characterization of pediatric germinomas. Citation Format: Holly B. Lindsay, Mari Kogiso, Lin Qi, Teo Wan Yee, Yulun Huang, Hua Mao, Frank Lin, Patricia Baxter, Jack M. Su, Keita Terashima, Laszlo Perlaky, Ching C. Lau, Donald W. Parsons, Murali Chintagumpala, Xiao-Nan Li. Establishment of patient tumor-derived orthotopic xenograft models of metastatic pediatric germinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1193. doi:10.1158/1538-7445.AM2014-1193