Raiber et al. Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma. npj Genome Medicine. Article number: 6 (2017) doi:10.1038/s41525-017-0007-6
Researchers at the University of Cambridge have, for the first time, created single base resolution maps of whole genomes, methylomes and hydroxylmethylomes for matched human glioblastoma and tumour margin samples. This ground-breaking study, published in npj Genomic Medicine, provides new insights into the interrelation of genetics and epigenetic variations.
Previous studies using bisulfite converted DNA to measure combined levels of 5mC and 5hmC have led to genome-wide hypomethylation being regarded as an epigenetic hallmark of tumorigenesis. However, by using both bisulfite and oxidative bisulfite (oxBS) converted DNA to discriminate between 5mC and 5hmC, the team instead identified global hypermethylation in the tumour. This result suggests that data obtained from bisulfite-only approaches need to be re-interpreted.
Notably, the team also observed 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.
The reference (epi)-genome generated in this research provides a human model system for future studies that aim to explore the link between genetic and epigenetic variations in cancer progression and may foster diagnostic approaches in the future.