Genetic Map Adds to Cancer Research

A recent study headed by researchers at the Harvard-affiliated Dana-Farber Cancer Institute has identified a complete map of the genetic regions that may influence how estrogen contributes to breast cancer—results that could advance clinical treatment for breast cancer patients.

The study identifies the molecular “control panels,” which consists of thousands of on-off switches for genes, that may be part of the mechanism by which estrogen regulates breast cancer.

The findings—to be published in Nature Genetics this month—may help individualize treatment for breast cancer patients and provide additional options for those patients resistant to drugs currently used for treatment, according to the senior author, Harvard Medical School (HMS) Associate Professor of Medicine Myles A. Brown.

Estrogen contributes to tumor cell growth via its role in binding to a protein net known as the estrogen receptor (ER), located in the nucleus of 70 percent of breast cancer cells. When estrogen attaches to this receptor, the binding initiates a flurry of activity in genes directly related to cell growth and division.

Many cancerous cells have a disproportionately high number of ERs in their nuclei, facilitating the rapid propagation of these malignant cells.

Current drug-based treatment works by blocking ERs, thus slowing or stopping tumor growth.

The study identified sections of DNA known as control regions, portions of genes pertaining to cell growth and division that bind to the ER. These control regions remotely activate or inhibit the function of the gene.

The researchers created a map of all of these regions—several thousand in total. Since genes have multiple control regions, the map indicates that approximately one thousand genes are influenced by the binding of estrogen to the ER, according to a statement released by Dana-Farber.

The map itself was created through a novel technique known as ChIP on chip, which involves purifying regions of the genome that take orders directly from the ER, and placing the regions on microarray chips containing the complete human genome.

This process allowed researchers to contrast the two sets of genetic information, and to see which genes are expressed as a result of interaction with the ER, according to the statement.

Brown said that the technique allowed the researchers to identify the location of the relevant genes within the genome as a whole.

This research may have important applications for cancer treatment.

Brown explained that there is potential for variation among different women in the genetic regions that bind to the ER, resulting in variation in the ease with which estrogen binds to the ER and thus variation in the degree of malignant cell growth.

The ability to predict these differences would help doctors customize treatment plans for cancer patients based on their individual biology, according to Brown.

The study also indicated the presence of other factors that cooperate with the ER to regulate genes, factors that “might themselves become targets for new therapies,” Brown wrote in an e-mail.

Brown said that his lab is conducting research to examine whether cancer drugs change the structure of the receptive sites on the ER. If this is the case, then new drugs can be created as tumors gain resistance to current drugs.

The research was conducted in conjunction with researchers from HMS, Brown University, and Affymetrix in Santa Clara, Calif.