Mitochondrial DNA (mtDNA) methylation in normal mucosa, adenoma and colorectal cancer patient samples

Altered mitochondrial function and large-scale changes to DNA methylation patterns in the nuclear genome are both hallmarks of colorectal cancer (CRC). Mitochondria have multiple copies of a 16kb circular genome that contains genes that are vital for their function. While DNA methylation is known to alter the nuclear genome in CRC, it is not clear whether it could have a similar influence in mtDNA; indeed, currently, the issue of mitochondrial genome (mtDNA) methylation occurs is controversial.To investigate the relationship between DNA methylation and mitochondria in CRC, we performed Whole Genome Bisulphite Sequencing of mtDNA-enriched DNA from 4 normal mucosa and paired adenoma, and 2 paired normal mucosa and CRC samples.Overall methylation of CG dinucleotides in the nuclear genome was reduced in adenomas (68%) compared to normal tissue (75%). Methylation in mtDNA was low (1%) in both normal and adenoma tissue but we observed clusters of higher methylation at the rRNA genes.