Genomic dynamics associated with malignant transformation in IDH1 mutated gliomas

Genomic mechanism responsible for malignant transformation has been a major concern in glioma research, but differing conclusions have been drawn based on diverse study conditions. Therefore, it is indispensable to secure the direct evidence using longitudinal samples in the same patient. We have analyzed genomic data using next generation sequencing technology for the serial samples from 3 patients with IDH1 mutated gliomas who had undergone progression of the disease from histologically benign to malignant phenotype. Comprehensive analysis of genomic dynamics in clonal evolution during the malignant transformation and validation with public database revealed alterations in regulating machinery of gene expression involving spliceosomal complex, transcriptional factor, or chromatin remodeler. And, consequential expression changes implied activation of genes associated with restoration of stemness of the cancer cells. Despite being limited to small number of cases, this analysis provides direct example of genomic changes responsible for malignant transformation in gliomas.