It seems that cancer is joining the minimalist trend, and has recently been caught sporting a universal and distinct DNA methylation signature. A talented team from John Hopkins lead by epi-gurus Andrew Feinberg and Rafael Irizarry show that large hypomethylated blocks are a defining feature in a number of different human solid tumors.
These hypomethylated blocks also happen to overlap locations rich in heterochromatic LOCKs (large organized chromatin lysine- modifications) and LADs (lamin-associated domains) and can occur in single copy genes. By looking at a broad array of tumors (10 breast, 28 colon, 9 lung, 38 thyroid, 18 pancreas cancers, and 5 pancreas neuroendocrine tumors), matched controls, and premalignant lesions the team made some universal findings, while also developing a new statistical approach that lets you identify large hypomethylated blocks during your run of the 450k discovery mill. Here’s what they found:
- Hypomethylated blocks are a universal feature of common solid human cancer.
- Blocks occur at the earliest stage of premalignant tumors.
- The hypomethylated blocks progress along with cancer.
The work confirms previous findings from numerous groups showing disruptions to CpG islands in cancer (hypermethylated island bodies and hypomethylated shores) and shows that these regions are enriched in the newly discovered hypomethylated blocks.
Interestingly, the hypomethylated blocks are characterized by a flattening of the methylation signal within and flanking the islands. Also adding to the power of the finding, genes that show the greatest variation in expression between individuals are also enriched in the hypomethylated blocks. This leaves the crew concluding that hypomethylated blocks are “a universal defining epigenetic alteration in human cancer, at least for common solid tumors.”
Check out cancers diverse methylation universe in Genome Medicine, August 2014