Orthotopic Meningioma Rat Model Exhibits Morphological and Immunohistochemical Congruency and Epigenetic Concordance with Benign Primary Patient-derived Tumors

Meningiomas are the most common primary central nervous system tumor. Clinical trials have failed to support effective medical treatments, despite initially promising animal studies. A key issue could be that available experimental models fail to mimic the clinical situation. Hence, there is a need for meningioma models with high translational value for understanding pathophysiology and tests of possible medical treatments. Resemblance between models and clinical meningiomas should be optimized with respect to morphology, immunohistochemistry and epigenetic factors, which we aimed to do. Third passage primary patient-derived benign meningiomas were implanted intracranially in athymic nude rats. The animals were euthanized after three months. We found intra- and intertumoral variability in terms of tumor take rate (79.5% for superficially implanted cells and 25% for deeply implanted cells) and xenograft sizes. There were close resemblance between primary tumors and xenografts in morphology and immunohistochemistry. Furthermore, we performed DNA-methylation using the EPIC 850 K array on three pairs of primary tumors and xenografts. Copy number variation profiles and correlation plots on CpGs showed a high degree of similarities between primary tumors and corresponding xenografts. On differential methylation analysis, most probes were insignificant (866,074), 25 were hypermethylated, and 382 were hypomethylated, where no significant differentially methylated regions were revealed.