The molecular characteristics of low-grade and high-grade areas in desmoplastic infantile astrocytoma/ganglioglioma.

Abstract

AIMS:

Desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIGs) are rare brain tumours of infancy. A distinctive feature of their histopathology is a combination of low-grade and high-grade features. Most DIA/DIGs can be surgically resected and have a good prognosis. However, high-grade features often dominate recurrent tumours, some of which have a poor outcome. In this study, we test the hypothesis that low-grade and high-grade areas in DIA/DIGs have distinct molecular characteristics.

METHODS:

Tissue samples from microdissected low-grade and high-grade areas in 12 DIA/DIGs were analysed by DNA methylation profiling, whole exome sequencing, RNA sequencing and immunohistochemistry to search for potential differences at multiple molecular levels.

RESULTS:

Copy number variants among tumours and between the two morphologically distinct areas were infrequent. No recurrent genetic alterations were identified across the tumour series, and high-grade areas did not have additional genetic alterations to explain their distinct morphology or biological behaviour. However, high-grade areas showed relative hypomethylation in genes downstream of the transcription factors SOX9 and LEF1 and evidence of a core SOX9 transcription network alongside activation of the BMP, WNT and MAPK signalling pathways.

CONCLUSIONS:

This study contributes to our knowledge of molecular genetic alterations in DIA/DIGs, uncovers molecular differences between the two distinct cell populations in these tumours and suggests potential therapeutic targets among the more proliferative cell population in DIA/DIGs.

• Authors: Jason Chiang, Xiaoyu Li, Hongjian Jin, Gang Wu, Tong Lin, David W Ellison
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 48 Issue 4 Pg. e12801 (06 2022) ISSN: 1365-2990 [Electronic] England
• PMID: 35191090 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 British Neuropathological Society.

Topics

• Astrocytoma (genetics, pathology)
• Brain Neoplasms (genetics, pathology)
• Ganglioglioma (genetics, pathology)
• Humans
• Infant
• Magnetic Resonance Imaging
• Mutation
• Exome Sequencing