GSE193129
The molecular characteristics of low-grade and high-grade areas in desmoplastic infantile astrocytoma / ganglioglioma [RNA-seq]
A distinctive feature of the histopathology of desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIGs) is a combination of low-grade and high-grade areas. In this study, we test the hypothesis that low-grade and high-grade areas in DIA/DIGs have distinct molecular characteristics. Tissue samples from microdissected low-grade and high-grade areas in 12 DIA/DIGs were analyzed by DNA methylome profiling, whole exome sequencing, RNA sequencing, and immunohistochemistry. Copy number variants among the tumours and between the two morphologically distinct areas were infrequent. No recurrent genetic alterations were identified across the tumor series, and high-grade areas did not have additional genetic alterations to explain their distinct morphology or biological behaviour. However, high-grade areas showed relative hypomethylation in genes downstream of the transcription factors SOX9 and LEF1 and evidence of a core SOX9 transcription network alongside activation of the BMP, WNT, and MAPK signalling pathways. This study contributes to our knowledge of molecular genetic alterations in DIA/DIGs, uncovers molecular differences between the two distinct cell populations in these tumours, and suggests potential therapeutic targets among the more proliferative cell population in DIA/DIGs. Overall design: RNA-seq from the microdissected low-grade and high-grade areas of 12 DIA/DIG FFPE samples