Engenharia reversa de redes regulatórias do meduloblastoma e inferência de reguladores mestres

Abstract

Medulloblastoma (MB) is a cancer of the cerebellum occurring most frequently in the pediatric population. This tumor is classified into four distinct molecular subgroups (WNT, SHH, group 3 and group 4), each one also presenting unique clinical features. Some medulloblastoma epigenetic drivers have been reported by some studies, although the inference of regulatory networks and master regulators have been mentioned only once. Here, we inferred the transcriptional regulatory networks of SHH, group 3 and group 4 subgroups and recognized 10 regulatory units as master regulators and differentially methylated regulons, simultaneously, for all investigated subgroups, subsequently named as the “regulons of interest”. The activity pattern of these regulons was observed to vary across subgroups. KEGG pathway enrichment analysis was also done, considering the content of all regulons of interest in each regulatory network. Two KEGG terms were found concomitantly for all investigated subgroups. This work contributes to the comprehension of the medulloblastoma regulome, identifying prospective master regulators, analyzing their methylome and pointing to potential therapeutic targets.