Gene that repairs DNA found to cause breast cancer when mutated

By targeting stem cells carrying the mutated gene, scientists hope to treat cancer.

Researchers have identified yet another rogue gene responsible for breast cancer. This one can be used in early diagnosis and treatment of cancer, the team believes.

The gene GT198 known to repair DNA, regulate stem cells, cell suicide and turning other genes off and on, appears to cause breast cancer when mutated. Stem cells with the mutated gene were seen to trigger breast cancer instead of making healthy breast tissue.

"This gene mutation can be in both the blood and the tumor tissue of patients, and in the tissue, it's in high percentages," said Dr. Lan Ko, the study's co-author who is cancer biologist in the Department of Pathology at the Medical College of Georgia at Augusta University and at the Georgia Cancer Center at AU. "We believe that once this gene is mutated, it induces the tumor to grow."

The work published in the American Journal of Pathology was done on an international sampling from 254 cases of breast cancer in pre-and postmenopausal women.

The gene is normally regulated by the hormone estrogen, Ko said. But once mutated, it does not need estrogen for tumour production.

Breast tissue includes fat cells, fibroblasts which make the framework for tissue; pericytes in blood vessels and myoepithelial cells comprising the outer layer of the ductal system through which milk flows. The mutated GT198 directly affects stem cells that make all these various components of breast tissue.

All cells in the body have the GT198 gene but most adult cells don't express it. In the breast it may be transiently expressed in a pregnant woman preparing for milk production or in the case of breast injury. Males express it in the testes.

The team plans to look at treatments that target the misguided stem cells instead of only addressing the cancerous breast tissue. Ko said, "We think the way to treat breast cancer is to target the progenitor cells. We want to kill these cells that are feeding the tumor rather than just killing the tumor cells, which is less effective."

In a 2013 study Ko and her colleagues showed the gene could also be a source for ovarian cancer.

Ductal breast cancer, which is in the ducts that carry milk, is the most common type of breast cancer and lobular carcinoma, which begins in the milk-producing glands, is the second most common. Most breast cancer comes from the cells that line those ducts.

BRCA1 and 2, genes that work as tumor suppressors and also repair DNA damage, were the first known risk factor genes for familial breast cancer as well as ovarian and other cancers.