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Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence.

Publication ,  Journal Article
Sexton-Oates, A; Dodgshun, A; Hovestadt, V; Jones, DTW; Ashley, DM; Sullivan, M; MacGregor, D; Saffery, R
Published in: Mol Oncol
August 2018

Childhood pilocytic astrocytomas (PA) 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 DNA methylation profiling to inform tumour biology and to predict behaviour in paediatric PA. Genome-wide DNA methylation profiles were generated for 117 paediatric PAs. Using a combination of analyses, we identified DNA 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 DNA 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 NEUROG1 and NR2E1 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 PAs, 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.

Duke Scholars

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Published In

Mol Oncol

DOI

EISSN

1878-0261

Publication Date

August 2018

Volume

12

Issue

8

Start / End Page

1219 / 1232

Location

United States

Related Subject Headings

  • Receptors, Cytoplasmic and Nuclear
  • Proto-Oncogene Proteins B-raf
  • Progression-Free Survival
  • Prognosis
  • Orphan Nuclear Receptors
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Mutation
  • Humans
  • Gene Expression Regulation, Neoplastic
 

Citation

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Sexton-Oates, A., Dodgshun, A., Hovestadt, V., Jones, D. T. W., Ashley, D. M., Sullivan, M., … Saffery, R. (2018). Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence. Mol Oncol, 12(8), 1219–1232. https://doi.org/10.1002/1878-0261.12062
Sexton-Oates, Alexandra, Andrew Dodgshun, Volker Hovestadt, David T. W. Jones, David M. Ashley, Michael Sullivan, Duncan MacGregor, and Richard Saffery. “Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence.Mol Oncol 12, no. 8 (August 2018): 1219–32. https://doi.org/10.1002/1878-0261.12062.
Sexton-Oates A, Dodgshun A, Hovestadt V, Jones DTW, Ashley DM, Sullivan M, et al. Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence. Mol Oncol. 2018 Aug;12(8):1219–32.
Sexton-Oates, Alexandra, et al. “Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence.Mol Oncol, vol. 12, no. 8, Aug. 2018, pp. 1219–32. Pubmed, doi:10.1002/1878-0261.12062.
Sexton-Oates A, Dodgshun A, Hovestadt V, Jones DTW, Ashley DM, Sullivan M, MacGregor D, Saffery R. Methylation profiling of paediatric pilocytic astrocytoma reveals variants specifically associated with tumour location and predictive of recurrence. Mol Oncol. 2018 Aug;12(8):1219–1232.

Published In

Mol Oncol

DOI

EISSN

1878-0261

Publication Date

August 2018

Volume

12

Issue

8

Start / End Page

1219 / 1232

Location

United States

Related Subject Headings

  • Receptors, Cytoplasmic and Nuclear
  • Proto-Oncogene Proteins B-raf
  • Progression-Free Survival
  • Prognosis
  • Orphan Nuclear Receptors
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Mutation
  • Humans
  • Gene Expression Regulation, Neoplastic