Pan-Cancer Analysis Reveals Presence of Pronounced DNA Methylation Drift In Cpg Island Methylator Phenotype Clusters

Abstract

Aim: To provide characteristics of major genomic correlates in CpG island methylator phenotype-high (CIMP-H) subgroups in relation to corresponding non-CIMP-H subgroups by use of phenotypic, DNA methylation and RNAseq data. Materials & methods: Twenty-three datasets generated by The Cancer Genome Atlas project encompassing over 7200 unique samples were analyzed. We identified 23 CIMP-H clusters by use of unsupervised clustering. Results & conclusion: More than 90% of CIMP-H clusters were significantly associated with accelerated epigenetic mitotic clock, demethylation of enhancer sites, backbone and repetitive sequences. Pronounced epigenetic drift observed in majority of CIMP-H subgroups may be related to increased cell division rate, which leads to expansion of DNA methylation errors. This may explain pan-cancer mechanism of establishing CIMP-H in majority of tissue types.

Keywords::

• backbone
• cancer
• clustering
• CpG island
• DNA methylation
• epigenetic drift
• Illumina 450k
• methylator phenotype
• repetitive sequences

Acknowledgements

The authors are grateful to patients and TCGA. This study was performed in frame of Wroclaw Medical University statutory activities (ST-919).

Financial & competing interests disclosure

P Karpinski’s research was supported by internal funding from the Foundation of Wroclaw Medical University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2017-0070

Additional information

Funding

P Karpinski’s research was supported by internal funding from the Foundation of Wroclaw Medical University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.