Defect of breast cancer gene discovered Cells unable to correct 'mistakes,' scientists say

August 14, 1998|By NEW YORK TIMES NEWS SERVICE

Scientists at the University of North Carolina have made an important discovery about how defects in one of the two breast cancer genes, BRCA1, raise the risk of the disease: They leave cells without the normal ability to correct certain mistakes that commonly occur in their genetic machinery.

Scientists and experts elsewhere say the finding has potentially important clinical implications for people known to carry the defective gene in their cells. The information, reported in today's issue of the journal Science, will add to the understanding of how cancer starts and what might be done to prevent it. The fTC lead author of the study, graduate student Lori Gowen, said, "This is the first direct evidence of a function for this tumor-suppressor gene, and it helps to explain how the gene may be involved in cancer."

The study, done in specially altered cells derived from a mouse, showed that the BRCA1 gene directly or indirectly participates in a process called transcription-coupled repair, a rapid means of correcting mistakes that occur in the DNA of other genes.

When people make a mistake writing with a pencil, they use an eraser, on the typewriter they use white-out and on the computer, the delete button. When an error occurs in the DNA of a gene, cells rely on an error-specific repair mechanism to knock out the errant information.

In today's report, Gowen, Dr. Steven Leadon and colleagues report that the normal task of BRCA1, one of the two genes known to be involved in hereditary cancers of the breast and ovary, is to repair DNA damage caused by oxidation, a process that occurs continually in the body in the course of normal metabolism and that can result from exposure to outside agents like radiation.

When BRCA1 is defective, it is unable to repair oxidative DNA damage, the most common insult to the genetic material of cells. A defective BRCA1 gene is responsible for about 5 percent of breast cancers and can affect men as well as women.

Pub Date: 8/14/98

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