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Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma

Accepted version
Peer-reviewed

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Authors

Raiber, EA 
Beraldi, D 
Martinez Cuesta, Sergio  ORCID logo  https://orcid.org/0000-0001-9806-2805
McInroy, GR 
Kingsbury, Z 

Abstract

Aberrant genetic and epigenetic variations drive malignant transformation and are hallmarks of cancer. Using PCR-free sample preparation we achieved the first in-depth whole genome (hydroxyl)-methylcytosine, single-base-resolution maps from a glioblastoma tumour/margin sample of a patient. Our data provide new insights into how genetic and epigenetic variations are interrelated. In the tumour, global hypermethylation with a depletion of 5-hydroxymethylcytosine was observed. The majority of single nucleotide variations were identified as cytosine-to-thymine deamination products within CpG context, where cytosine was preferentially methylated in the margin. Notably, we observe that cells neighbouring tumour cells display epigenetic alterations characteristic of the tumour itself although genetically they appear “normal”. This shows the potential transfer of epigenetic information between cells that contributes to the intratumour heterogeneity of glioblastoma. Together, our reference (epi)-genome provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression.

Description

Keywords

0604 Genetics, 1112 Oncology and Carcinogenesis, Biomedical, Basic Science, Cancer, Human Genome, Genetics, Rare Diseases, Brain Cancer, Brain Disorders, Cancer, 2.1 Biological and endogenous factors

Journal Title

Genomic Medicine

Conference Name

Journal ISSN

2056-7944
2056-7944

Volume Title

2

Publisher

Nature Publishing Group
Sponsorship
Cancer Research UK (C14303/A17197)
Brain Tumour Charity (10/136)
Wellcome Trust (099232/Z/12/Z)
Cancer Research UK (CB4160)
Cancer Research UK 236 (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z)