The molecular characteristics of low-grade and high-grade areas in desmoplastic infantile astrocytoma / ganglioglioma [methylation array]
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PROVIDER: PRJNA795425 | ENA |
REPOSITORIES: ENA
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Project description:A distinctive feature of the histopathology of desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIGs) is a combination of low-grade and high-grade areas. In this study, we test the hypothesis that low-grade and high-grade areas in DIA/DIGs have distinct molecular characteristics. Tissue samples from microdissected low-grade and high-grade areas in 12 DIA/DIGs were analyzed by DNA methylome profiling, whole exome sequencing, RNA sequencing, and immunohistochemistry. Copy number variants among the tumours and between the two morphologically distinct areas were infrequent. No recurrent genetic alterations were identified across the tumor 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. 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.
2022-05-24 | GSE193196 | GEO
Project description:A distinctive feature of the histopathology of desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIGs) is a combination of low-grade and high-grade areas. In this study, we test the hypothesis that low-grade and high-grade areas in DIA/DIGs have distinct molecular characteristics. Tissue samples from microdissected low-grade and high-grade areas in 12 DIA/DIGs were analyzed by DNA methylome profiling, whole exome sequencing, RNA sequencing, and immunohistochemistry. Copy number variants among the tumours and between the two morphologically distinct areas were infrequent. No recurrent genetic alterations were identified across the tumor 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. 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.
2022-05-24 | GSE193129 | GEO
Project description:The molecular characteristics of low-grade and high-grade areas in desmoplastic infantile astrocytoma / ganglioglioma [RNA-seq]
| PRJNA795049 | ENA
Project description:AimsDesmoplastic 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.MethodsTissue 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.ResultsCopy 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.ConclusionsThis 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.
| S-EPMC9202004 | biostudies-literature
Project description:Survival in the majority of high grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors. A better understanding of the biological factors associated with long-term survival in HGA would aid development of more effective therapy and prognostication. We used microarray gene expression profiling of 26 patient surgical samples with known clinical outcomes to discover novel prognostic markers.
2011-10-31 | GSE33331 | GEO
Project description:Copy number analysis of 21 paediatric low-grade astrocytomas identified a discrete copy number gain of 1.9Mb in chromosome band 7q34. The gain was present in 12/14 cerebellar pilocytic astrocytomas. Subsequent analysis of tumour cDNA indentified a novel gene fusion between KIAA1549 and BRAF in these tumours. Copy number analysis of 21 paediatric low-grade astrocytomas using the Affymetrix GeneChip Human Mapping 250K Nsp Array. This study comprised 14 pilocytic astrocytomas, 4 diffuse astrocytomas, one pilomyxoid astrocytoma, one pilomyxoid glioma and one pleomorphic xanthoastrocytoma. Tumours were compared to the mean of two normal male DNA controls.
2010-04-09 | E-GEOD-14960 | biostudies-arrayexpress
Project description:Survival in the majority of high grade astrocytoma (HGA) patients is very poor, with only a rare population of long-term survivors. A better understanding of the biological factors associated with long-term survival in HGA would aid development of more effective therapy and prognostication. We used microarray gene expression profiling of 26 patient surgical samples with known clinical outcomes to discover novel prognostic markers. Gene expression profiles were generated from surgical tumor samples using Affymetrix HG-U133plus2 chips. All genes were correlated with survival as a continuous variable in order to identify ontologys associated with risk of recurrence.
2011-10-31 | E-GEOD-33331 | biostudies-arrayexpress
Project description:Single Nucleotide Variations in a tissue sample of Desmoplastic Infantile Ganglioma
2022-02-17 | PRJEB50889 | EVA
Project description:Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain.
2011-03-23 | GSE22927 | GEO