Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma
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....
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2017-03-01
|
Series: | npj Genomic Medicine |
Online Access: | https://doi.org/10.1038/s41525-017-0007-6 |
id |
doaj-d643e54649364e6b98631c4333afedd9 |
---|---|
record_format |
Article |
spelling |
doaj-d643e54649364e6b98631c4333afedd92020-12-08T13:47:45ZengNature Publishing Groupnpj Genomic Medicine2056-79442017-03-01211710.1038/s41525-017-0007-6Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastomaEun-Ang Raiber0Dario Beraldi1Sergio Martínez Cuesta2Gordon R. McInroy3Zoya Kingsbury4Jennifer Becq5Terena James6Margarida Lopes7Kieren Allinson8Sarah Field9Sean Humphray10Thomas Santarius11Colin Watts12David Bentley13Shankar Balasubramanian14Cancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeCancer Research UK Cambridge Institute, University of CambridgeDepartment of Chemistry, University of CambridgeIllumina Ltd.Illumina Ltd.Illumina Ltd.Illumina Ltd.Department of Pathology, Addenbrooke’s Hospital, Cambridge University HospitalsCancer Research UK Cambridge Institute, University of CambridgeIllumina Ltd.Department of Clinical Neurosciences, Division of Neurosurgery, University of CambridgeDepartment of Clinical Neurosciences, Division of Neurosurgery, University of CambridgeIllumina Ltd.Cancer Research UK Cambridge Institute, University of CambridgeAbstract 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.https://doi.org/10.1038/s41525-017-0007-6 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eun-Ang Raiber Dario Beraldi Sergio Martínez Cuesta Gordon R. McInroy Zoya Kingsbury Jennifer Becq Terena James Margarida Lopes Kieren Allinson Sarah Field Sean Humphray Thomas Santarius Colin Watts David Bentley Shankar Balasubramanian |
spellingShingle |
Eun-Ang Raiber Dario Beraldi Sergio Martínez Cuesta Gordon R. McInroy Zoya Kingsbury Jennifer Becq Terena James Margarida Lopes Kieren Allinson Sarah Field Sean Humphray Thomas Santarius Colin Watts David Bentley Shankar Balasubramanian Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma npj Genomic Medicine |
author_facet |
Eun-Ang Raiber Dario Beraldi Sergio Martínez Cuesta Gordon R. McInroy Zoya Kingsbury Jennifer Becq Terena James Margarida Lopes Kieren Allinson Sarah Field Sean Humphray Thomas Santarius Colin Watts David Bentley Shankar Balasubramanian |
author_sort |
Eun-Ang Raiber |
title |
Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma |
title_short |
Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma |
title_full |
Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma |
title_fullStr |
Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma |
title_full_unstemmed |
Base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma |
title_sort |
base resolution maps reveal the importance of 5-hydroxymethylcytosine in a human glioblastoma |
publisher |
Nature Publishing Group |
series |
npj Genomic Medicine |
issn |
2056-7944 |
publishDate |
2017-03-01 |
description |
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. |
url |
https://doi.org/10.1038/s41525-017-0007-6 |
work_keys_str_mv |
AT eunangraiber baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT darioberaldi baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT sergiomartinezcuesta baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT gordonrmcinroy baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT zoyakingsbury baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT jenniferbecq baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT terenajames baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT margaridalopes baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT kierenallinson baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT sarahfield baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT seanhumphray baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT thomassantarius baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT colinwatts baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT davidbentley baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma AT shankarbalasubramanian baseresolutionmapsrevealtheimportanceof5hydroxymethylcytosineinahumanglioblastoma |
_version_ |
1724389310586683392 |