Using the latest gene sequencing tools to examine so-called epigenetic influences on the DNA makeup of colon cancer, a Johns Hopkins team says its results suggest cancer treatment might eventually be more tolerable and successful if therapies could focus on helping cancer cells get back to normal in addition to strategies for killing them.
In a report published June 26 in Nature Genetics, the investigators focused on a particular epigenetic biochemical signature known as methylation, which silences genes. Although not part of a gene's central DNA sequence, it is copied when a cell divides, perpetuating its activity.
By comparing the epigenomes of eight human tissue samples -- three from noncancerous colon tissue, three from colon tumors and two from polyps (early-stage colon cancer) -- the team found that in all the colon tumors the defining characteristic was a universally "chaotic" pattern of methylation. In noncancerous tissue, they found methylation occurring in well-defined places, either as small "islands" of methylation or huge methylated "blocks" that collectively encompassed at least a third of the genome.
"In the cancer tissue we saw that the once-precise boundaries of the islands had shifted or disappeared altogether, and the start and end points of the sites appeared unregulated," says Andrew Feinberg, M.D., M.P.H., professor of molecular medicine and director of the Center for Epigenetics at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Sciences. "We also saw a loss of methylation, presumably increasing the randomness of gene function within them."
"What seems to define cancer at the epigenetic level may be simple and common, namely chaos that seems to be universal," he adds.
The researchers noted that cells in their normal colon tissue samples stayed methylated at around the 80 percent level for large (and previously unexamined) blocks of the epigenome. By com
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions