Ohio State Documents Steps in Development of Breast Cancer

One of the first models of breast cancer showing a multi-step process which involves more than one cell type has been produced by researchers at the Ohio State University Comprehensive Cancer Center using a new laser-microdissection technology which permits dissection of tumors one cell at a time.

This is the first documentation of the sequence of events taking place in the formation of breast cancer, including which "hits" happen first and which specific cells are involved, according to the study published in Human Molecular Genetics.

"This is almost paradigm-breaking," said Dr. Charis Eng, director of the Clinical Cancer Genetics Program at Ohio State and lead author of the study. "In breast cancer, the alterations that lead to malignancy are thought to occur only in the epithelial cells of the breast. We have shown for the first time that genetic mutations can occur with some frequency in the stromal (surrounding) cells, too."

Researchers used laser capture microdissection (LCM) to study the tissue of 41 invasive breast tumors. LCM uses a laser beam only 7.5 microns wide as a knife, enabling scientists to isolate cancer cells from normal cells and to separate epithelial cells from stromal cells.

"Before LCM, the study of cancer genetics entailed grinding up a lump of tumor comprising a mixture of cells and examining the 'mixed bag' of cells for gene alterations," said Eng. "We really couldn't attribute genetic changes to any one cell type. LCM allows us to do that."

Researchers were then able to extract the DNA from each cell set, measuring the loss of heterozygosity (LOG), a gene alteration indicator.

"LOH is a technical indicator of the loss of a tumor suppressor gene," said Eng. "A tumor suppressor gene is like the brakes of a car, which keep the cell from reproducing over and over again. Normally, a cell has a pair of suppressors working for it. LOH simply means at least one -- more maybe both sets of brakes -- are broken."

LOH was frequent in both cell types, with the higher frequency of LOH in the epithelial tissue suggesting that mutations there might precede changes in the surrounding structures. "In the field of human cancer genetics, it is believed that markers with the highest frequency of LOH represent those with the earliest genetic alterations, the so-called first "hits" and the one with the lowest frequency of LOH, the latest "hit" in carcinogenesis."

"On top of that, we were able to associate certain changes in the epithelial cells with corresponding changes in the stroma," reported Eng. "We used to think that the surrounding structure of the cancer cell was just a silent bystander in the process of carcinogenesis. Now we know better."

Other Sources: Ohio State University Medical Center