October 27, 1998

Johns Hopkins scientists have found a genetic alteration associated with common forms of colon cancer in patients' normal cells. The same abnormality, called loss of imprinting (LOI), also appears, the researchers say, in a significant number of healthy people, offering a possibility of predicting as many as 40 percent of new colon cancer cases before they start.

"It's the first cancer-related genetic alteration found at high frequency in healthy people," says Andrew P. Feinberg, M.D., who with Hengmi Cui, Ph.D., led the study appearing in this month's Nature Medicine. By contrast, APC and HNPCC, the known colon cancer genes that predict high risk of the disease, together account for less than 3 percent of new cases.

In the study, the Hopkins team analyzed both tumors and normal parts of the colon in 30 patients with colon cancer, looking for loss of imprinting. LOI -- a recently discovered phenomenon with a strong tie to cancer and other diseases -- refers to an abnormal switching-on or off of genes.

People inherit copies of the same gene from both parents, and both genes or sets of genes work in tandem in a person's cells. In normal development, in a process called imprinting, the copy from one parent, in certain genes, is turned off. This inherited preferential silencing usually holds throughout all cells in a person's body.

In their investigations of cancer, however, researchers have learned that such genes can lose their imprinting. "We know there is a link between LOI and cancer," Feinberg says, "because we've repeatedly found LOI in cancers, notably in genes that either encourage cell growth or that suppress cancer." Earlier work by Feinberg and by others has showed, for example, that LOI appears frequently in Wilms' tumor, the most common non-blood cancer in children.

In this new study, researchers focused on a specific growth-promoting gene called IGF2 (for in
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Contact: Marjorie Centofanti
mcentofanti@jhmi.edu
410-955-8725
Johns Hopkins Medical Institutions
3-Nov-1998