E-A Raiber, D Beraldi, S Martínez Cuesta, GR McInroy, Z Kingsbury, J Becq, T James, M Lopes, K Allinson, S Field, S Humphray, T Santarius, C Watts, D Bentley, S Balasubramanian
Journal name: 
NPJ Genom Med
Citation info: 
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.
Research group: 
Balasubramanian Group
E-pub date: 
31 Aug 2017
Users with this publication listed: 
Eun-Ang Raiber
Sergio Martinez Cuesta
Shankar Balasubramanian