Eintrag weiter verarbeiten
Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence
Gespeichert in:
| Zeitschriftentitel: | Molecular Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Molecular Oncology, 12, 2018, 8, S. 1219-1232 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| Zusammenfassung: | <jats:p>Childhood pilocytic astrocytomas (<jats:styled-content style="fixed-case">PA</jats:styled-content>) are low‐grade tumours with an excellent prognosis. However, a minority, particularly those in surgically inaccessible locations, have poorer long‐term outcome. At present, it is unclear whether anatomical location in isolation, or in combination with underlying biological variation, determines clinical behaviour. Here, we have tested the utility of <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation profiling to inform tumour biology and to predict behaviour in paediatric <jats:styled-content style="fixed-case">PA</jats:styled-content>. Genome‐wide <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation profiles were generated for 117 paediatric <jats:styled-content style="fixed-case">PA</jats:styled-content>s. Using a combination of analyses, we identified <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation variants specific to tumour location and predictive of behaviour. Receiver‐operating characteristic analysis was used to test the predictive utility of clinical and/or <jats:styled-content style="fixed-case">DNA</jats:styled-content> methylation features to classify tumour behaviour at diagnosis. Unsupervised analysis distinguished three methylation clusters associated with tumour location (cortical, midline and infratentorial). Differential methylation of 5404 sites identified enrichment of genes involved in ‘embryonic nervous system development’. Specific hypermethylation of <jats:italic><jats:styled-content style="fixed-case">NEUROG</jats:styled-content>1</jats:italic> and <jats:italic><jats:styled-content style="fixed-case">NR</jats:styled-content>2E1</jats:italic> was identified as a feature of cortical tumours. A highly accurate method to classify tumours according to behaviour, which combined three clinical features (age, location and extent of resection) and methylation level at a single site, was identified. Our findings show location‐specific epigenetic profiles for <jats:styled-content style="fixed-case">PA</jats:styled-content>s, potentially reflecting their cell type of origin. This may account for differences in clinical behaviour according to location independent of histopathology. We also defined an accurate method to predict tumour behaviour at diagnosis. This warrants further testing in similar patient cohorts.</jats:p> |
|---|---|
| Umfang: | 1219-1232 |
| ISSN: |
1574-7891
1878-0261 |
| DOI: | 10.1002/1878-0261.12062 |