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We’re getting a better idea of how moles turn into melanoma, and environment is key

The genetic changes that drive the emergence of skin cancer seem to be caused by environmental factors.

Alexandru Micu by Alexandru Micu
November 24, 2021
in Genetics, Health, News, Science

New research is upending what we knew about the link between skin moles and melanoma.

Image via Pxhere.

Moles and melanomas are both types of skin tumors, and they originate from the same cells — the pigment-producing melanocytes. However, moles are harmless, and melanomas are a type of cancer that can easily become deadly if left untreated. The close relationship between them has been investigated in the past, in a bid to understand the emergence of melanomas.

New research at the Huntsman Cancer Institute (HCI) , the University of Utah, and the University of California San Francisco (UCSF) comes to throw a wrench into our current understanding of that link. According to the findings, our current “oncogene-induced senescence” model of the emergence of melanomas isn’t accurate. The research aligns with other recent findings on this topic, and propose a different mechanism for the emergence of skin cancer.

Environmentally-driven

“A number of 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 has remained elusive.”

Melanocytes are tasked with producing the pigments in our skin which protect us from harmful solar radiation. Changes (mutations) in one specific gene in the genome of melanocytes, known as BRAF gene mutations, are heavily associated with moles; such mutations are found in over 75% of skin moles. At the same time, BRAF gene mutations are encountered in 50% of melanoma cases.

Our working theory up to now — the oncogene-induced senescence– was that when melanocytes develop the BRAFV600E mutation, it blocks their ability to divide, which turns them into a mole. However, when other mutations develop alongside BRAFV600E, melanocytes can start dividing uncontrollably, thus developing into cancer.

The team investigated mole- and melanoma tissues donated by patients at the UCSF Dermatology clinic in San Francisco or the HCI Dermatology clinic in Salt Lake City. Their analysis revolved around two methods known as transcriptomic profiling and digital holographic cytometry. The first one allows them to determine molecular differences between the cells in moles and those in melanomas. The second one was used to track changes inside individual cells.

“We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes become melanomas,” says Judson-Torres.

The team reports that melanocytes don’t need to have mutations besides BRAFV600E to morph into melanoma. What does play a part, however, are environmental factors, transmitted to the melanocytes through the skin cells around them. Depending on exactly what signals they’re getting from their environment, melanocytes express different genes, making them either stop dividing or divide uncontrollably.

“Origins of melanoma being dependent on environmental signals gives a new outlook in prevention and treatment,” says Judson-Torres. “It also plays a role in trying to combat melanoma by preventing and targeting genetic mutations. We might also be able to combat melanoma by changing the environment.”

The authors hope that their findings will help researchers get a better idea of the biomarkers that can predict the emergence of melanoma at earlier stages than possible today. Furthermore, the results here today can also pave the way to more effective topical medicine that can prevent melanoma, or delay its progress.

The paper “BRAFV600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB” has been published in the journal eLife.

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  4. Vitamin D supplements may lower the risk of melanoma
  5. Five or more blistering sunburns before the age of 20 increase melanoma risk by 80 percent
Tags: geneticsmelanomamoleskin

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