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From mole to melanoma

In a recent study, researchers have explained how common moles form and how they can change into melanoma.

Melanoma vs moles

Melanoma is a type of skin cancer that arises from damaged melanocytes. Over half of all melanomas are driven by an activating mutation in the BRAF proto-oncogene (BRAFV600E). However, when a melanocyte acquires this mutation, the cell does not immediately transition into cancer. In fact, it typically undergoes clonal proliferation followed by stable arrest. This results in a benign skin lesion, which is more commonly known as a mole. While BRAFV600E continues to be expressed, the majority of moles actually remain innocuous for the lifespan of the individual. This suggests that these cells have robust intrinsic defences against hyperproliferation. It is currently unclear as to why this same genetic mutation in the BRAF gene can have such different consequences in moles and melanoma.

One prevailing theory has been oncogene-induced senescence (permanent cell-cycle arrest). However, recent observations have challenged this theory, which means it is important to investigate other mechanisms to understand the establishment and maintenance of proliferation arrest in moles.

Reversible mitotic arrest

In a recent study, published in eLife, researchers used genetic approaches to study melanocytes from moles and melanomas. More specifically, the team compared the transcriptomes of melanocytes from healthy skin, moles and melanomas.

From this, they identified a set of microRNAs that were present at higher levels in moles than in melanomas. The increased levels of two microRNAs—MIR211-5p and MIR328-3p— stopped the cells from growing and dividing by inhibiting a gene called AURKB.  This suggests that these microRNAs play a role in halting the growth of moles.

The researchers also introduced this mutated form of BRAF into melanocytes which stopped the cells from growing and dividing. However, changing the environment surrounding these cells reversed the effects and allowed the melanocytes to resume dividing. This indicates that BRAFV600E induces a proliferation arrest that is reversible and conditional.

Together, this data presents an alternative molecular mechanism for mole formation that is consistent with both experimental and clinical observations. The team are now interested in using this data to better understand potential treatments that could reduce the risk of melanoma, delay its development or stop its recurrence.

 Robert Judson-Torres, Researcher at the Huntsman Cancer Institute, said:

“Origins of melanoma being dependent on environmental signals gives a new outlook in prevention and treatment.

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.”

Image credit: canva

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Cancer / Cancer Research / Environment