Tumor suppressor genes

Published on January 31, 2021   40 min
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My name is Fred Bunz. I'm an associate professor of Radiation Oncology here in the Department of Radiation Oncology and Molecular Radiation Sciences at the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins School of Medicine in Baltimore, Maryland. The topic of today's lecture will be tumor suppressor genes.
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In order to appreciate the function and concept of the tumor suppressor gene, it's necessary to first understand the properties of oncogenes which were the first type of cancer genes to be discovered. The idea of a dominantly acting cancer gene first arose at the beginning of the 20th century from some seminal observations by a virologist named Peyton Rous. Rous had discovered a distinct form of tumor that would affect guinea hens.
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These tumors were very aggressive. Rous found that if he ground up the tumors, pass them through a small pore filter and inject with a filtrate into young hens, he could recreate and actually serially transmit the tumor, so the tumor would re-grow in the infected chickens. This was right around the time shortly after the discovery of viruses, so Rous inferred that the tumor had been transmitted by a virus. This was the first experimental evidence that cancers could be transmitted via dominantly acting genes or genetic elements.
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In subsequent decades, investigators used a variety of strategies to isolate oncogenes, all of them depending on the dominant phenotypes of activated oncogenes. In this experiment, normal human DNA would be sheared and delivered to cells and culture with no effect. However, when shear DNA from a cancer cell line would be delivered to cells growing in culture, a proportion of the cells would grow abnormally and assume cancer-related phenotypes as shown in this illustration. Subsequent studies would allow the oncogene from this genomic DNA to be isolated. So the critical observation here was oncogenes could be isolated on the basis of their effects on cell growth, on the basis of their function.