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The Transcriptomic Landscape of Pediatric Astrocytoma

ABSTRACT: Tumors of the central nervous system are the most common solid neoplasia during human childhood, representing one of the leading causes of cancer-related mortality. Tumors that originate from astrocyte cells (astrocytoma) in the brain are the most frequently found. According to their histological and pathological features, these tumors are classified into four categories. However, recently an extra layer of molecular classification of the tumorigenesis-associated genes IDH1/2 and H3F3A has been incorporated into the classification guidelines. While mutations in H3F3A are exclusively found in a subtype of pediatric astrocytoma grade IV, mutations in IDH1/2 are very rare in children younger than 14 years old. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied however focusing on the study of the transcriptomic profile of the different grades of astrocytoma (including the additional layer of molecular classification) in pediatric populations are scarce. Therefore, we have profiled the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196694 | GEO | 2022/10/25

REPOSITORIES: GEO

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Project description:Purpose: To define copy number alterations and gene expression signatures underlying pediatric high-grade glioma (HGG). Patients and Methods: We conducted a high-resolution analysis of genomic imbalances in 78 de novo pediatric HGG, including 7 diffuse intrinsic pontine gliomas, and 10 HGG cases arising in children who received cranial irradiation for a previous cancer, using Affymetrix 500K GeneChips. Gene expression signatures for 53 tumors were analyzed with Affymetrix U133v2 arrays. Results were compared with publicly available data from adult tumors. Results: Pediatric and adult glioblastoma were clearly distinguished by frequent gain of chromosome 1q (30% vs 9%) and lower frequency of chromosome 7 gain (13% vs 74%), respectively. The most common focal amplifications also differed, with PDGFRA and EGFR predominant in childhood and adult populations respectively. These common alterations in pediatric HGG were detected at higher frequency in irradiation-induced tumors, suggesting that these are initiating events in childhood gliomagenesis. CDKN2A was the most common tumor suppressor gene targeted by homozygous deletion in pediatric HGG. No IDH1 hotspot mutations were found in pediatric tumors, highlighting molecular differences in pathogenesis between childhood HGG and adult secondary glioblastoma. Integrated copy number and gene expression data indicated that deregulated PDGFRA signaling plays a major role in pediatric HGG. Conclusions: Integrated molecular profiling showed substantial differences in the molecular features underlying pediatric and adult HGG, indicating that findings in adult tumors cannot be simply extrapolated to younger patients. PDGFRA may be a useful target for pediatric HGG including diffuse pontine gliomas. Keywords: disease state analysis 78 samples for SNP analysis, including 10 samples arising in children who received cranial irradiation for a previous cancer and 7 diffuse pontine gliomas; 53 of them with gene expression analysis; 2 tumor grades To have access to SNP CEL files, please contact Dr. Suzanne Baker (suzzane.baker@stjude.org).

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The Transcriptomic Landscape of Pediatric Astrocytoma

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