A novel modeling of high-grade transformation in IDH mutant glioma

Background. High-grade transformation (HT) is a key feature of IDH-mutant glioma, which is inevitable and unpredictable. Both genomic and metabolomic landscapes are going through dynamic processes during the transformation. Although HT phenomena have been observed clinically, the research of mechanisms underlying HT have been limited by the lack of in vitro models that can recapitulate the evolution of malignant transformation. Methods. Here we established a unique pair of cell lines that was generated using tumor samples from the same patient at different stages of the disease. 403L cell line was obtained when patient's tumor was astrocytoma, WHO grade 2 and 403H cell line was obtained when the tumor was transformed to astrocytoma, WHO grade 4. Using genomic, transcriptomic, and metabolomic analyses, the two cell models have been characterized extensively. The cell lines have been used to establish orthotopic xenograft models of the disease. Overall design: Comparative gene expression profiling analysis of RNA-seq data for 403H & 403L cells. Each group was comprised of 3 biological replicates.