Abstract 4812: A novel set of patient-derived orthotopic xenograft (PDOX) models of primary and recurrent intracranial meningioma

Abstract

Abstract Background: Meningioma is the most common brain tumors in adults. Despite the overall benign nature of meningioma, cranial-base tumors are difficult to achieve complete resection while others exhibit progression and aggressive profiles characterized by high recurrence rates, pleomorphic histology, and resistance to standard treatment. The lack of clinically relevant animal models is blocking the development of novel therapies. Here, we report our establishment of orthotopic xenograft mouse models and in vitro culture systems from surgical specimens of primary and recurrent meningiomas. Material and Methods: 6 primary surgical samples (3 WHO grade I and 3 atypical), and 4 recurrent samples (1 WHO grade I, 2 atypical and 1 anaplastic meningiomas) were obtained from meningioma patients. Tumor tissues were dissociated into single cells and directly implanted into right cranial base of NOD/SCID mice (1x105 cells/mouse). Primary cultures were initiated in serum-free and traditional FBS-based media. Tumor growth was monitored by small animal MRI. Pathologic features of the PDOX models and the matched patient tumors were compared with standard H&E and immunohistochemical staining. Molecular fidelity of PDOX tumor was examined through genomic analysis and comparison with the parental tumors. Results: Three of the 10 tumors were not tumorigenic, and xenograft tumor formation from 5 additional samples is pending. Growth of intracranial (cranial base) xenograft was confirmed in two samples derived from the same patient diagnosed as atypical meningioma (K029MEN) and progressed as anaplastic meningioma at recurrence (K037MEN). These patient derived orthotopic xenografts (PDOX) have since been serially subtransplanted in mouse brains for generation 2 and can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors replicated histopathological features (invasion, high proliferation and increased microvessel density) of their parental tumors. Genomic analysis is being performed to examine the similarities between parental tumors and the corresponding orthotopic xenograft tumors and the discrepancies between the primary and the recurrent tumor-derived models. In vitro growth of K029MEN and K037MEN as neurospheres and monolayer were maintained for 2 months and passage for 10 times. Additionally, cells from K030MEN, a WHO grade I meningioma, has been passaged as monolayer for more than 30 times. Conclusion: A novel set of meningioma PDOX models derived from matching primary and recurrent tumor was established. The xenograft tumors replicated the histopathological and key molecular features of the original patient tumors, providing a unique opportunity to understand the biology of malignant meningiomas and to conduct preclinical drug testing. Note: This abstract was not presented at the meeting. Citation Format: Huiyuan Zhang, Lin Qi, Yuchen Du, Frank K. Braun, Mari Kogiso, Sibo Zhao, Holly B. Lindsay, Sarah G. Injac, Patricia A. Baxter, Jack M. Su, Akash J. Patel, Xiao-nan Li, Baylor College of Medicine. A novel set of patient-derived orthotopic xenograft (PDOX) models of primary and recurrent intracranial meningioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4812. doi:10.1158/1538-7445.AM2017-4812