Feinberg says the findings could mean that current efforts to simply identify methylation markers as signals of cancer or targets of cancer therapy may be misleading or worse, won't do the job at all. An alternative would be a new method that detects epigenetic chaos universally in any cancer epigenome.
The team designed a custom test to compare about 20 noncancerous tissue samples to 20 samples from each of a variety of tumors as they investigated thousands of methylation sites for colon, breast, lung, kidney and thyroid cancers. They found that, here again, methylation was well-regulated in the normal tissues, almost always occurring within a limited range of variability. However, in the very same specific places of the epigenome characterized by chaos in colon cancer cells, all the other cancerous tissues examined by the team showed distinctly variable and "chaotic" levels of methylation variation.
"Maybe the big lesson learned from our observation of this universal chaos is that we may need to think not so much about just killing cancer cells, but also about ways of helping cancer cells figure out how to be what they're supposed to be, and re-educate them so they can stay truer to their normal identities," Feinberg says.
From the cancer cells' "perspective," Feinberg says, the chaos is helpful, endowing tumors with the ability to turn genes on and off in an uncontrolled way, and making cancer cells adaptable enough to live in all different kinds of environments, spread and thrive in foreign tissue.
"The regions of epigenetic chaos where methylation appears wildly variable in at least five different common cancers are -- not so coincidentally -- the very same as those that during normal development are important in controlling cell differentiation, or what particular ce
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions