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Aug 25, 2010

New Cell Lines for Anaplastic Thyroid Cancer Created

  • Mayo Clinic researchers have created a new set of laboratory anaplastic thyroid cancer (ATC) cells, derived from tumors donated by patients. They developed four ATC cell lines, each with a different set of molecular mutations driving this aggressive cancer.

    Details are published in the August 25 online issue of the Journal of Clinical Endocrinology & Metabolism. The researchers are sharing the new ATC cells with the international community, says the study's co-principal author, John Copland, Ph.D., a cancer biologist at the Mayo Clinic campus at Jacksonville.

    The cell-line development project was prompted by researchers at Mayo Clinic when they discovered several years ago that laboratory samples of ATC they were using to help find new treatments were probably some other kind of cancer. They soon realized that the situation in their lab was common throughout the world. Up to half of the cell lines that were supposed to originate from patients with this rare thyroid cancer were either colon cancer or melanoma.

    "Since cell lines are immortal and can live forever, they are critical to research, and a major issue is cell-line contamination leading to misidentification and drawing incorrect conclusions for specific cancers," Dr. Copland says. "We provide higher standards for characterizing new cell lines at the genomic and molecular level that can be traced back to the originating tumor tissue."

    Studies on the newly created cell line reportedly shows detailed molecular fingerprinting that links genetic mutations found in the patients' tumors to the cell lines that are derived from these tumors. If any question arises in the future as to whether these lines have become contaminated by other cancers, researchers can use the Mayo Clinic data to confirm the origin of the cells.

    The study also tested five different drugs in these new cell lines for potential benefit. The researchers found that all of these agents—everything from an approved cholesterol-lowering agent to experimental transferase inhibitors—reactivated a tumor suppressor gene called RhoB, leading to growth suppression. Mayo researchers, led by Dr. Copland, had previously discovered that RhoB function was missing in ATC cells, as it is in some other cancers.

    Robert Smallridge, M.D., a co-principal author, is currently conducting a Phase I trial testing an agent that can turn the tumor suppressor function back on. Because thyroid cancers are uncommon and anaplastic thyroid cancer is exceedingly rare—fewer than 600 new ATC cases a year in the U.S.—Dr. Smallridge asks every patient having surgery for thyroid cancer at Mayo Clinic for a tumor sample. Other surgeons around the country have sent Laura Marlow, the study’s lead investigator, tumor samples in her quest to create new cell lines for thyroid cancer.

    Using tumor samples from this collaboration, it took two years and several tries to create the four new lines, Marlow says. "These cells are very difficult to grow and to maintain because of their chromosomal instability." Marlow had to derive a new formula for the media that the cells live on in their culture dishes, a recipe that is special for this kind of cancer and which is reproduced in the study publication. The article also identifies multiple genetic and phenotypic tests that will uniquely identify each cell line now and in the future, she says.


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