Model co-created by UCLA Health’s Dr. Beth Karlan provides platform for scientists to study factors that lead to cancer development in BRCA1 mutation carriers

The lifetime risk of developing ovarian cancer is less than 2% for the general female population, but for women who carry a mutation in the BRCA1 gene, estimated risk is between 35% and 70%.

Beth Karlan, MD, a specialist in gynecologic oncology and the director of Cancer Population Genetics at UCLA Jonsson Comprehensive Cancer Center, co-led a study in which cancer researchers and stem cell scientists used cells from ovarian cancer patients who had a BRCA1 mutation to create tissues, called organoids, modeling tissues of fallopian tubes.

Dr. Beth Karlan (Photo by Joshua Sudock/UCLA Health)

“From peripheral white blood cells that were immortalized – manipulated to proliferate indefinitely – we made induced pluripotent stem cells,” Dr. Karlan said. “We then created conditions for those cells to differentiate into organoids that recapitulate the serous fallopian tube cells that are the origin of ovarian cancer.”

Dr. Karlan said the findings, published in the Dec. 28, 2021 Cell Reports, offer several opportunities for researchers. The organoid model provides a platform for scientists to study factors that lead to cancer development in BRCA1 mutation carriers as well as factors that might prevent transformation to cancer. It also enables researchers to test therapeutic interventions on organoids that recapitulate ovarian cancer.

“Ovarian cancer, the leading cause of gynecologic cancer deaths in the U.S., often remains undetected until it has reached advanced stages and has spread beyond the ovaries,” Dr. Karlan said. “The establishment of fallopian tube organoids created from women with and without BRCA1 mutations may help predict which individuals will develop ovarian cancer and help identify interventions that may be able to prevent cancer.

"Currently, surgery to remove the fallopian tubes and ovaries is the most effective preventative intervention," she said. "But these fallopian tube organoids provide a model that contains all the genes of the person who provided the blood sample, and they can be used to test the effectiveness of multiple drugs or combinations of drugs to prevent the development of cancer. This is a major step toward our ultimate goal of providing truly personalized medicine and precision prevention.”

The study supports recent research suggesting that ovarian cancer most frequently originates from the cells lining the fallopian tubes. In fact, compared to organoids created from healthy women without a BRCA1 mutation, the organoids with the BRCA1 mutation spontaneously developed multiple cellular abnormalities that are consistent with cancer development.

Read Dr. Karlan's Cell Reports article.

Sandy Van is the author of this article.


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