Moles and melanomas are skin tumors that come from the same cell called melanocytes. The difference is that moles are usually harmless, whereas melanomas are cancerous and often fatal without treatment.
Moles and melanomas: On “senescence induced by oncogenes”.
In a published study Today in eLife, Robert Judson-Torres, Ph.D., a researcher at the Huntsman Cancer Institute (HCI). And assistant professor of dermatology and cancer sciences at the University of Utah (U of U). Explain how common moles and melanomas form and why moles can turn into melanoma.
Melanocytes are cells that give skin its color to protect it from the sun’s rays. Specific changes in the DNA sequence of melanocytes, called BRAF gene mutations, are found in more than 75% of the moles. The same change is also found in 50% of melanomas and is common in cancers such as colon and lung.
It was thought that when melanocytes only had the BRAFV600E mutation, the cell stopped dividing, resulting in a mole. When melanocytes have other BRAFV600E mutations, they divide uncontrollably and become melanoma. This model is called “oncogene-induced senescence.”
“Several studies have challenged this model in recent years,” says Judson-Torres. “These studies have provided excellent data to suggest that the oncogene-induced senescence model does not explain mole formation, but what they have all lacked is an alternative explanation, which remains elusive.”
Melanocytes that develop into melanoma do not need to have additional mutations
With the help of collaborators from HCI and the University of California, San Francisco. The study team took patient-donated moles and melanomas and used transcriptomic profiling and digital holographic cytometry. The transcriptomic profile allows researchers to determine the molecular differences between moles and melanomas. Digital holographic cytometry helps researchers track changes in human cells.
“We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes turn into melanomas,” says Judson-Torres.
The study shows that the melanocytes that develop into melanoma do not need to have additional mutations. But they are actually affected by environmental signaling, when cells receive signals from the environment in the skin around them that gives them direction. Melanocytes express genes in different environments, telling them to divide uncontrollably or to stop dividing altogether.
Better understand possible topical agents to reduce the risk of melanoma
“The origins of melanoma that depend on environmental cues provide a new perspective on prevention and treatment,” says Judson-Torres. “It also plays a role in trying to fight melanoma by preventing and targeting genetic mutations. We could also fight melanoma by changing the environment. “
These findings create a basis for the investigation of possible melanoma biomarkers, allowing doctors to detect cancerous changes in the blood at an earlier stage.
Researchers are also interested in using this data to better understand potential topical agents to reduce melanoma risk, delay development or stop recurrence, and detect melanoma early.
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