Subtle changes in normal genes implicated in breast cancer

Scientists found that benign cells surrounding breast cancers undergo epigenetic modifications. The altered gene function causes the microenvironment cells to signal proliferation and increased aggression in the breast tumor cells.

Kornelia Polyak, M.D., Ph.D., is senior author of the paper, which was posted as an advance online publication on the Nature Genetics Web site. Min Hu, Ph.D., of Dana-Farber, is first author of the paper.

Polyak’s team had shown hyperactivity in genes in the breast milk microenvironment, even when their DNA was unaltered during cell reproduction. She suspected inheritance of the ‘methylation state’ of the DNA. Gene activity can be regulated by the chemical switch process methylation, and the on-off pattern of methylation in a cell’s genes is hereditary, even when the DNA remains unchanged. This is an example of epigenetic modification.

Cancer is often associated with abnormal methylation of DNA. Polyak’s team, looking to obtain the methylation pattern of a cell’s entire genome, developed the method Methylation Specific Digital Karyotyping (MSDK). Polyak and her colleague profiled the entire genome in weeks, far less time than with conventional methods.

Using MSDK, the scientists tested epithelial and myoepithelial cells lining cancerous breast ducts, and the surrounding cells, known as stoma, including fibroblasts. They found that in all of these cell types, gene expression was altered by epigenetic methylation changes that were absent in normal breast tissue.