TMOD-10. ESTABLISHMENT OF ADULT AND PEDIATRIC BRAZILIAN PRE-CLINICAL MODELS FOR HIGH-GRADE GLIOMAS

Abstract High-grade gliomas (HGG) are the most aggressive brain tumors, necessitating robust and representative preclinical models for therapeutic research. We established primary cultures and patient-derived xenograft models from three pediatric high-grade gliomas (pHGG) and one adult IDH wild-type glioblastoma (GBM IDHwt) Brazilian patients. The first pHGG case, from an 11-year-old with PDGFRA (c.1977C>G) and TP53 (c.637C>T) mutations, led to the development of the HCB570 primary culture, PDX and patient-derived orthotopic xenograft (PDOX) OXP9. The second pHGG, from an 11-year-old with CMMRD syndrome and MSH6 germline mutation, resulted in the HCB589 primary culture, PDX and PDOX OXP22. The third pHGG case, from a 14-year-old with diffuse midline glioma harboring an H3F3A mutation, established the HCB604 primary culture and PDX OXP32. The HCB612 primary culture and PDX GBM1, were established from an adult patient with GBM IDHwt, TERT mutated, with no MGMT promoter methylated. The primary cultures showed varied proliferative rates, with an average doubling time of 55 hours. All cultures demonstrated colony-formating capability, with an average IC50 of 750µM for temozolomide (TMZ) exposure. Immunohistochemical and EPIC methylation profiles confirmed that the PDX models closely resemble the patient features. Our establishment of diverse preclinical models, including those derived from patients with rare genetic conditions such as CMMRD, provides valuable insights into HGG pathogenesis and potential therapeutic strategies. The present Brazilian patient-derived models enrich glioma research inclusion diversity and foster future personalized treatment approaches.