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March 28, 2024

Researchers investigate the origin of cancer

By SCOTT ZHENG | February 18, 2016

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NICHD/cc-by-2.0 Researchers observed the development of melanoma tumors in genetically altered zebra fish.

Cancer is a notoriously difficult disease to understand.

For a long time, researchers thought that genes would mutate randomly and cause cells to rapidly divide and proliferate. Then, as mutated cells divide, more mutations would be formed, ultimately causing cancer.

But just having mutations turned out not to be enough — some cells have mutations, yet they do not divide and proliferate the way cancer cells do.

Scientists have had trouble with advancing cancer treatment and prevention techniques due to the unknown origins of cancer. However, new research at Boston Children’s Hospital could help researchers come up with treatments that can prevent cells from becoming cancerous.

This new research shows that adult cells can revert to an embryonic state.

“We found that the beginning of cancer occurs after activation of an oncogene or loss of a tumor suppressor and involves a change that takes a single cell back to a stem cell state,” Charles Kaufman, a researcher in the Stem Cell Research Program at Boston Children’s Hospital, said in a press release.

Leonard Zon, the director of the Stem Cell Research Program at Boston Children’s Hospital, started studying the origins of cancer 10 years ago using zebrafish. Zebrafish are commonly used in genetic research due to their genetic similarity to humans and their ability to produce a large amount of offspring. This gives researchers the ability to “create” rare events, like cancer.

Zon’s team genetically altered a gene in zebrafish so that the skin pigment cells inside the fish would turn fluorescent green if crestin, a gene that signals the presence of stem cells, is activated. Typically this gene is inactive after embryonic development, but for unknown reasons, the genes are reactivated in some cells.

Kaufman observed 30 zebrafish that exhibited fluorescent green cells. In each zebrafish that had these green cells, a melanoma, the most dangerous form of skin cancer, had formed. Kaufman was even able to see a single green-glowing cell divide until it became a tumor in two such zebrafish.

“Every so often we would see a green spot on a fish. When we followed them, they became tumors 100 percent of the time,” Zon said in a press release.

The rarity of a melanoma forming in the zebrafish population that Zon’s lab used was similar to the chance of a melanoma forming in the human population, suggesting that the origin of melanoma in humans is most likely through the same uncommon mechanism. The fact that primitive cells, like embryonic stem cells, are more proliferative than mature cells is further evidence that this mechanism is key to the development of cancer.

Zon proposed that cancer is developed when either an oncogene inside the cell is activated or a tumor suppressor gene is silenced, along with the cell reverting to an embryonic state, which allows it to start dividing. Zon hypothesized that most, if not all, types of cancer originate like this.

It is still unclear why certain cells revert to their embryonic states or what kinds of mutations are common in these cells. Also, there is no word on how much time remains after the cell reverts and before it divides and becomes a tumor mass. Still, this can be considered a major breakthrough in cancer research because it pinpoints how cancer originates, which could lead to new methods of preventing cancer from fully developing early on.

The next step in preventing cancer from being formed would be to create a test that spots mutated cells that have a tendency to revert back to stem cells. Once this is found, researchers could develop treatment methods of preventing the cells from dividing and becoming cancerous, or they could create a drug that kills the cells that are susceptible to reverting back to an embryonic stem cell state.


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