Epigenetic enzymes are among the prime suspects in the identity parade of genes responsible for the deregulation of the genome in cancer. But are the same epigenetic enzymes always found at the scene of the crime? A new analysis from a team of international researchers led by Andrew Teschendorff identifies three epigenetic enzymes that can only be described as serial offenders in the pathogenesis of cancer.
The deregulation of epigenetic enzymes in cancer leads to alterations in chromatin configuration, DNA methylation, and gene expression and helps cancers to evolve more quickly, promoting invasion and metastasis. Pharmacologically targeting these enzymes is possible, so finding the most important oncogenic or tumor suppressor enzymes has major implications for cancer therapy.
Teschendorff’s team examined the expression of 212 epigenetic enzymes, including all the main writers, readers, and editors of the epigenome using RNA-Seq data from 10 different types of cancer from The Cancer Genome Atlas. They also analyzed DNA methylome data from these cancers to pinpoint the epigenetic enzymes responsible for wreaking havoc on patterns of methylation.
- The study demonstrated the deregulated expression of 62 epigenetic enzymes (37 upregulated and 25 downregulated) in at least 8 out of the 10 cancer types studied.
- The analysis of global hypermethylation and hypomethylation in the cancers found that the two were not well correlated, suggesting that they are independent processes in tumor progression under the control of separate epigenetic enzymes.
- The study also found a link between 18 epigenetic enzymes and instability in DNA methylation across cancer types.
- Network modeling identified UHRF1 and WHSC1 as the criminal masterminds in DNA hypermethylation, and the loss of CBX7 as a key driver of hypomethylation.
Intriguingly, the deregulation of these genes appears to affect methylation at the same loci across different cancer types, showing that these enzymes leave a characteristic signature at the scene of the crime.
The authors conclude, “These findings show that there are universal patterns of epigenomic deregulation that transcend cancer types”.
Read the full case file at Genome Biology, July 2015.