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Study reveals genetic driver for rare metaplastic breast cancer

New mouse model gives researchers insight into rare form of triple-negative breast cancer.

By Amy Wallace
Study reveals genetic driver for rare metaplastic breast cancer
Mammary tumors caused by deleting CCN6 look like metaplastic carcinoma.Researchers at the University of Michigan have developed a new mouse model to identify key genetic driver in rare type of breast cancer. Photo courtesy University of Michigan Health System

ANN ARBOR, Mich., Jan. 6 (UPI) -- Researchers from the University of Michigan Comprehensive Cancer Center have found a key genetic driver for a rare form of breast cancer.

Dr. Celina Kleer, Harold A. Oberman Collegiate Professor of Pathology and director of the Breast Pathology Program at the University of Michigan Comprehensive Cancer Center, has been studying how the CCN6 protein affects breast cancer development for more than a decade.

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Kleer and her team examined the effects of the deletion of CCN6 from the mammary glands in mice. The results showed delayed development and mammary glands that did not develop properly at different ages in mice.

"After a year, the mice started to form mammary gland tumors," Kleer said, in a press release. "These tumors looked identical to human metaplastic breast cancer, with the same characteristics. That was very exciting."

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Metaplastic breast cancer is a very rare and aggressive subtype of triple-negative breast cancer. Although 20 percent of all breast cancers are triple-negative, with only 1 percent being metaplastic.

"Metaplastic breast cancers are challenging to diagnose and treat," Kleer said. "In part, the difficulties stem from the lack of mouse models to study this disease."

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Metaplastic breast cancer cells are more mesenchymal, a cell state that enables them to move and invade. Researchers found that deleting CCN6 induced the epithelial process to mesenchymal transition.

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"Our hypothesis, based on years of experiments in our lab, was that knocking out this gene would induce breast cancer," Kleer said. "But we didn't know if knocking out CCN6 would be enough to unleash tumors, and if so, when, or what kind. Now we have a new mouse model, and a new way of studying metaplastic carcinomas, for which there's no other model."

Researchers studied tumors in mice in their new model and were able to identify several potential genes to target with therapeutics.

The study was published in Oncogene.

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