Giuseppina Catanzaro1, Elisabetta Ferretti2, Martina Chiacchiarini3, Zein Mersini Besharat3, Andrea Carai4, Evelina Miele5, Giada Del Baldo4, Angela Mastronuzzi5. 1. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. giuseppina.catanzaro@uniroma1.it. 2. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. elisabetta.ferretti@uniroma1.it. 3. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. 4. Neurosurgery Unit, Department of Neuroscience and Neurorehabilitation, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. 5. Department of Hematology/Oncology and Stem Cell Transplantation, IRCCS Bambino Gesu Children's Hospital, Rome, Italy.
Abstract
PURPOSE: Pediatric low-grade gliomas (pLGGs), the most frequent pediatric brain tumors, include different entities harboring distinct histological and molecular features. A major limitation in the development of treatments for these tumors is the absence of reliable in vitro models that would allow a better understanding of the molecular mechanisms that support their growth. Surgical excision is the primary treatment method and the extent of resection represents one of the strongest prognostic factors. pLGGs that cannot be completely resected are prone to recur and associated with relapses and extensive morbidities, thus remaining a major clinical challenge. METHODS: We established a protocol to successfully derive primary patient-derived pLGG cells and to fully characterize them from a molecular point of view. RESULTS: Primary patients-derived pLGG cells were extensively analyzed in order to confirm their reliability as cellular models. Specifically, we evaluated the growth rate, senescence, and molecular features, such as BRAF mutational status, methylation, and protein expression profile. CONCLUSION: This study extensively describes pLGG primary cellular models in terms of isolation, culture method, and molecular characterization that can be used to investigate pLGG biology.
PURPOSE: Pediatric low-grade gliomas (pLGGs), the most frequent pediatric brain tumors, include different entities harboring distinct histological and molecular features. A major limitation in the development of treatments for these tumors is the absence of reliable in vitro models that would allow a better understanding of the molecular mechanisms that support their growth. Surgical excision is the primary treatment method and the extent of resection represents one of the strongest prognostic factors. pLGGs that cannot be completely resected are prone to recur and associated with relapses and extensive morbidities, thus remaining a major clinical challenge. METHODS: We established a protocol to successfully derive primary patient-derived pLGG cells and to fully characterize them from a molecular point of view. RESULTS: Primary patients-derived pLGG cells were extensively analyzed in order to confirm their reliability as cellular models. Specifically, we evaluated the growth rate, senescence, and molecular features, such as BRAF mutational status, methylation, and protein expression profile. CONCLUSION: This study extensively describes pLGG primary cellular models in terms of isolation, culture method, and molecular characterization that can be used to investigate pLGG biology.