CR-16
EXPRESSION ANALYSIS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA REVEALS NETWORKS OF CO-EXPRESSED GENE NETWORKS ASSOCIATED WITH DIFFERENT CELLULAR COMPARTMENTS Free

Adamantinomatous craniopharyngiomas (ACPs) are a locally invasive tumour, frequently surrounded by florid glial and inflammatory reactive tissue. RNA sequencing was performed on 18 ACP and six control samples. Normalised expression counts of the 5000 most variably expressed genes underwent weighted gene co-expression network analysis (WCGNA) to establish modules of genes with a shared expression patterns across the samples. CTNNB1 mutations were identified in 15/17 (88%) cases with a mutation read frequency between 6 and 48%. This correlated with the histologically assessed percentage tumour content of samples. WGCNA identified several modules of interest. One module closely correlated with CTNNB1 mutation read frequency and is thought to reflect the gene signature of the tumour tissue. This included WNT pathway target genes (e.g. AXIN2) and other genes and potential therapeutic targets known to be expressed in ACP (e.g. EGFR, BMP4, TP63). In addition it included transcription factors required for ameloblast differentiation (including BCL11B, MSX2) suggesting of a common cellular origin. Another module, correlating with the presence of the histological feature “wet keratin”, included enamel proteins (AMELX, AMBN, ENAM) and keratins. A separate module correlated closely with the presence of glial tissue and GFAP expression whilst a fourth variably expressed across tumours was enriched for immune genes, particularly MHC molecules and markers of immune cells (including CD4, CD8 and CD68). Ongoing interrogation of this data and integration with similar data sets and clinical phenotype will help refine the molecular pathways activated in different cellular compartments in ACP and identify to novel therapeutic opportunities.