Adult grade II diffuse astrocytomas are genetically distinct from and more aggressive than their paediatric counterparts
| Autor: | Shani A. Mulholland, Deborah S. Malley, Samuel W. S. Openshaw, David T.W. Jones, Koichi Ichimura, Lu Liu, V. Peter Collins, Sally R. Lambert, L. Magnus Bäcklund, Danita M. Pearson |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty IDH1 Adolescent DNA Copy Number Variations Cellular differentiation DNA Mutational Analysis Biology Astrocytoma medicine.disease_cause Pathology and Forensic Medicine Cellular and Molecular Neuroscience Young Adult medicine Humans Child Gene DNA Modification Methylases Oligonucleotide Array Sequence Analysis Mutation Principal Component Analysis Brain Neoplasms Gene Expression Profiling Tumor Suppressor Proteins Age Factors Cell cycle DNA Methylation Middle Aged medicine.disease Survival Analysis Isocitrate Dehydrogenase Gene Expression Regulation Neoplastic DNA Repair Enzymes DNA methylation Female Neurology (clinical) BAMBI Tumor Suppressor Protein p53 |
| Zdroj: | Acta neuropathologica. 121(6) |
| ISSN: | 1432-0533 |
| Popis: | Diffuse astrocytomas (WHO grade II) typically present as slow-growing tumours showing significant cellular differentiation, but possessing a tendency towards malignant progression. They account for ~10% of all astrocytic tumours, with a peak incidence between 30 and 40 years of age. Median survival is reported as around 6–8 years. Mutations of TP53 and IDH1 have been described as genetic hallmarks, while copy number alterations are also relatively common. However, there is some evidence to suggest that these characteristics may vary with age. Here, we present an integrated clinicopathologic, genomic and transcriptomic analysis suggesting that paediatric and adult tumours are associated with distinct genetic signatures. For example, no childhood tumour showed mutation of IDH1/2 or TP53, virtually no copy number changes were seen, and MGMT methylation was absent. In contrast, adult tumours showed IDH1/2 mutation in 94% and TP53 mutation in 69% of cases, with multiple copy number alterations per case and hypermethylation of MGMT in the majority of tumours. These differences were associated with a worse prognosis in the adult patients. The expression array data also revealed a significant difference in the expression of a number of genes putatively involved in neural stem cell maintenance and CNS development, including DLL3, HES5, BMP2, TIMP1 and BAMBI. Genes involved in DNA replication and the cell cycle were also enriched in the adult tumours, suggesting that their more aggressive behaviour may be due to derivation from a more rapidly dividing, less differentiated cell type. |
| Databáze: | OpenAIRE |
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