Distinct molecular profile of diffuse cerebellar gliomas

AbstractRecent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation inSETD2 (n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive withH3F3A K27M mutation (n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function includingTP53 mutation (n = 9),PPM1D mutation (n = 2), and a novel type ofPPM1D fusion (n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those withH3F3A mutations were categorized in the “RTK I (PDGFRA)” group, and those DCGs had a gene expression signature that was highly associated withPDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brai...
Source: Acta Neuropathologica - Category: Neurology Source Type: research