Scientists know cancer develops over a period of years through a series of genetic changes or mutations. Scientists have also long accepted that these genetic mutations occur in a single cell type for any given cancer. But the sequence of events-which "hits" happen first, and which specific cells are involved-has not been clearly documented until now.

Writing in the September 1 issue of Human Molecular Genetics, a research team, led by Dr. Charis Eng, director of the Clinical Cancer Genetics Program at Ohio State, says it has uncovered evidence suggesting that genetic changes leading to breast cancer occur first in the epithelium of breast tissue, and then are followed by corresponding alterations in the surrounding structures, or stroma.

"This is almost paradigm-breaking," says Eng. "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 cells, too."

Utilizing laser capture microdissection, (LCM) investigators examined the tissue of 41 invasive breast cancers. In LCM technology, a laser beam only 7.5 microns in width - roughly one-tenth the size of a human hair -- acts as a "knife"- enabling researchers to isolate cancerous 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," says Eng. "We really couldn't attribute genetic changes to any one cell type. LCM allo
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Contact: Michelle Gailiun
gailiun.1@osu.edu
614-293-3737
Ohio State University Medical Center
1-Sep-2001