DNA methylation analysis of paediatric low-grade astrocytomas identifies a tumour-specific hypomethylation signature in pilocytic astrocytomas

Jeyapalan, Jennie, Doctor, G. T., Jones, Tania, Alberman, S. N., Tep, A., Haria, C. M., Schwalbe, Ed, Morley, Isabel, Hill, Alfred, LeCain, Magdalena, Ottaviani, Diego, Clifford, Steven, Qaddoumi, Ibrahim, Tatevossian, Ruth, Ellison, David and Sheer, Denise (2016) DNA methylation analysis of paediatric low-grade astrocytomas identifies a tumour-specific hypomethylation signature in pilocytic astrocytomas. Acta Neuropathologica Communications, 4 (1). p. 54. ISSN 2051-5960

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Official URL: http://dx.doi.org/10.1186/s40478-016-0323-6

Abstract

Low-grade gliomas (LGGs) account for about a third of all brain tumours in children. We conducted a detailed study of DNA methylation and gene expression to improve our understanding of the biology of pilocytic and diffuse astrocytomas. Pilocytic astrocytomas were found to have a distinctive signature at 315 CpG sites, of which 312 were hypomethylated and 3 were hypermethylated. Genomic analysis revealed that 182 of these sites are within annotated enhancers. The signature was not present in diffuse astrocytomas, or in published profiles of other brain tumours and normal brain tissue. The AP-1 transcription factor was predicted to bind within 200 bp of a subset of the 315 differentially methylated CpG sites; the AP-1 factors, FOS and FOSL1 were found to be up-regulated in pilocytic astrocytomas. We also analysed splice variants of the AP-1 target gene, CCND1, which encodes cell cycle regulator cyclin D1. CCND1a was found to be highly expressed in both pilocytic and diffuse astrocytomas, but diffuse astrocytomas have far higher expression of the oncogenic variant, CCND1b. These findings highlight novel genetic and epigenetic differences between pilocytic and diffuse astrocytoma, in addition to well-described alterations involving BRAF, MYB and FGFR1.

Item Type: Article
Additional Information: PMC4882864
Uncontrolled Keywords: diffuse astrocytomas, MAPK pathway, AP-1 targets, FOS, cyclin, D1 enhancers
Subjects: A300 Clinical Medicine
Department: Faculties > Health and Life Sciences > School of Life Sciences > Applied Sciences
Depositing User: Ay Okpokam
Date Deposited: 08 Nov 2016 12:29
Last Modified: 21 Dec 2016 18:33
URI: http://nrl.northumbria.ac.uk/id/eprint/28456

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