Expression profiles of 151 pediatric low-grade gliomas reveal molecular differences associated with location and histological subtype.

Neuro Oncol
Authors
Keywords
Abstract

BACKGROUND: Pediatric low-grade gliomas (PLGGs), the most frequent pediatric brain tumor, comprise a heterogeneous group of diseases. Recent genomic analyses suggest that these tumors are mostly driven by mitogene-activated protein kinase (MAPK) pathway alterations. However, little is known about the molecular characteristics inherent to their clinical and histological heterogeneity.

METHODS: We performed gene expression profiling on 151 paraffin-embedded PLGGs from different locations, ages, and histologies. Using unsupervised and supervised analyses, we compared molecular features with age, location, histology, and BRAF genomic status. We compared molecular differences with normal pediatric brain expression profiles to observe whether those patterns were mirrored in normal brain.

RESULTS: Unsupervised clustering distinguished 3 molecular groups that correlated with location in the brain and histological subtype. "Not otherwise specified" (NOS) tumors did not constitute a unified class. Supratentorial pilocytic astrocytomas (PAs) were significantly enriched with genes involved in pathways related to inflammatory activity compared with infratentorial tumors. Differences based on tumor location were not mirrored in location-dependent differences in expression within normal brain tissue. We identified significant differences between supratentorial PAs and diffuse astrocytomas as well as between supratentorial PAs and dysembryoplastic neuroepithelial tumors but not between supratentorial PAs and gangliogliomas. Similar expression patterns were observed between childhood and adolescent PAs. We identified differences between BRAF-duplicated and V600E-mutated tumors but not between primary and recurrent PLGGs.

CONCLUSION: Expression profiling of PLGGs reveals significant differences associated with tumor location, histology, and BRAF genomic status. Supratentorial PAs, in particular, are enriched in inflammatory pathways that appear to be tumor-related.

Year of Publication
2015
Journal
Neuro Oncol
Volume
17
Issue
11
Pages
1486-96
Date Published
2015 Nov
ISSN
1523-5866
URL
DOI
10.1093/neuonc/nov045
PubMed ID
25825052
PubMed Central ID
PMC4648300
Links
Grant list
P01 CA142536 / CA / NCI NIH HHS / United States
P01CA142536 / CA / NCI NIH HHS / United States
K08 NS087118 / NS / NINDS NIH HHS / United States
R01 DK099558 / DK / NIDDK NIH HHS / United States
P50 CA165962 / CA / NCI NIH HHS / United States
F32 CA180653 / CA / NCI NIH HHS / United States