The Transcriptomic Landscape of Pediatric Astrocytoma

Abstract

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes IDH1/2 and H3F3A has recently been incorporated into the classification guidelines. Although mutations in H3F3A are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in IDH1/2 genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method.

Role of Senescent Astrocytes in Health and Disease

“…In the panel to the left the senescent astrocyte affects a neuron already exhibiting severe neurodegenerative defects. In the panel to the right the senescent astrocyte induces different effects on special forms of glioblastoma and astrocytoma: increasing invasiveness (top arrow) [62,63]; and impairing proliferation (bottom arrow) [64]. The present astrocyte and neuron images are analogous to those of [23].…”

“…Increased invasiveness of this cancer is induced by expression of astrocyte-type genes [62] (Figure 2, right, top arrow). Various forms of identified astrocytoma cancers, developing from mis-regulated genes expressed together with altered biological pathways, are being investigated [63]. An additional example is a circumscribed low-grade astrocytic glioma.…”