Genome-wide hypomethylation and CpG hypermethylation are predictive of clinical outcome.
The extent to which the genome of a person’s liver cancer cells is modified by methylation correlates with clinical outcome, say researchers at the NIH.
The main causes of liver cancer are well defined. The molecular pathways activated in the disease, however, are not well characterized.
The NIH team analyzed the global levels of DNA methylation as well as the methylation status of 105 putative tumor suppressor genes of human liver cells. They found that tumor cells could be distinguished from healthy cells by genome-wide hypomethylation and CpG hypermethylation. Furthermore, both factors correlated with shorter survival.
The scientists also found that these changes in methylation were associated with selective inactivation of a number of genes including inhibitors of Ras and some inhibitors of angiogenesis.
The team suggests that in individuals with liver cancer, analyzing the methylation status of the genome of their tumor cells might have prognostic value. Either modifying genome methylation or targeting the Ras pathway might have therapeutic value, they add.
The study is published in the August issue of the Journal of Clinical Investigation.