The Current Focus of Cancer Research: From Oncogenes to DNA Methylation

In 1988, science journalist Natalie Angier published the groundbreaking book entitled Natural Obsessions. Angier’s book was a detailed look at the initial search for oncogenes. “In a few febrile years, researchers [have] revealed that the beginning of cancer lay not in a wholesale rewiring of the cell, but in a fistful of key genes [oncogenes] among the human quota of DNA,” wrote Angier, then summarizing the state of the science. 

Two decades later, the cancer research story has grown far more complex. It is true that the oncogenes and tumor suppressor genes, their growth-inhibiting counterpart, remain a main focus of cancer research. However, scientists no longer look single-mindedly for possible cancer-causing mutations in these genes. These scientists have widened their gaze and now scan the entire genome for a chemical modification called DNA methylation. The modification occurs when a methyl group attaches to a gene. The methyl tag alters the gene’s ability to interact with needed transcription regulators, thereby turning off the gene. Although DNA methylation often occurs naturally to make one inherited gene dominant over another, tumor cells often co-opt the methylation process early in their development, thus shutting down tumor suppressor genes and enabling their aberrant growth. 

In the June 15, 2008, issue of the journal Cancer Research, National Institute of Dental and Craniofacial Research (NIDCR) grantees add interesting new data to the DNA methylation story. Using a genome-wide scanning technique to analyze methylation patterns, the grantees discovered a set of 5 genes that are the most commonly methylated in squamous cell carcinoma of the head and neck. More than half of the 42 tumor samples analyzed in the study shared methylation between 2 of the 5 genes.

“The observation of co-methylation of certain candidate genes at distant loci [specific gene sites] is a significant finding,” the scientists noted. “This not only reveals the possibility for using comethylation for improved diagnosis but also suggests that the candidates described in the study may be involved in a similar pathway that is disrupted and epigenetically silenced in HNSCC [head and neck squamous cell carcinoma].”