The scientists found that non-cancerous cells surrounding young breast cancers -- the microenvironment -- undergo epigenetic modifications. (Epigenetic modifications affect genetic function and are passed along to the cell's offspring, but they don't alter a gene's actual structure or DNA.) The subtly altered gene function causes the microenvironment cells to send signals to the breast tumor cells to grow fast and become more aggressive.

"This is the first demonstration that epigenetic occur in the supportive cells of a tumor, and this further emphasizes that surrounding cells play an active role in cancer formation and growth," says Kornelia Polyak, MD, PhD. "These changes in the microenvironment may occur before breast duct cells undergo genetic changes that cause cancer, thus detecting the epigenetic alterations may be a means of early cancer diagnosis or even predicting cancer risk."

Polyak is senior author of the paper, which was posted this week as an advance online publication on the Nature Genetics web site, http://www.nature.com/ng. The first author of the paper is Min Hu, PhD, of Dana-Farber.

Polyak and her colleagues had previously shown that the genes in the microenvironment surrounding the breast's milk ducts were overactive, and that they continued to be overactive when their cells reproduced, even though their DNA had not been altered. She suspected that the methylation state of the cells' DNA was being inherited. A gene's activity can be regulated by a kind of chemical switch process, methylation, when units called methyl groups are added or removed from the gene's DNA. The on-off
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
13-Jul-2005