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More clarity about the origins of skin cancer

It was known that a mole can sometimes develop into melanoma (an aggressive form of skin cancer). How this happens was not known until then. Research by a team from the Netherlands Cancer Institute and the VU Medical Center clarified the mechanism of action in May 2012. A relevant study because skin cancer was then (is now – 2017) the most common form of cancer, of which 5% is caused by melanoma


In May 2012, according to reports from the KWF Cancer Fund, skin cancer was the most common form of cancer. And it was expected that the number of skin cancer patients would increase drastically in the coming years. And that indeed happened.There are different forms of skin cancer. 5% of these are caused by melanoma; However, 66% of skin cancer deaths are caused by melanoma. Their strong tendency to spread through blood and lymphatic vessels makes melanomas extra dangerous. Cure is only possible if the diagnosis is made in time. However, four out of ten patients present to the doctor too late and die within five years of diagnosis.

Birthmark can become melanoma

A birthmark is a collection of pigment-producing cells (melanocytes) in the skin. These cells are not dangerous in themselves, on the contrary, they protect us against the harmful influence of ultraviolet radiation. Moles are known to have a characteristic mutation (damage) to the oncogene BRAF (B-RAF is the gene linked to cancer formation). Despite this, most moles remain in a stable, non-growing state for many years. But sometimes a mole can develop into a dangerous skin cancer: melanoma. It was unknown for a long time how that process works.

The development in the cells of moles and melanomas

Researchers from the Netherlands Cancer Institute Antoni van Leeuwen Hospital (led by Prof. Daniël Peeper) and the VU Medical Center (led by Prof. Wolter Mooi) showed that both the birthmark cells and the malignant melanoma cells had the same specific BRAF mutation. They also found that moles contained high levels of PTEN (a protein that plays a role in tumor suppression), but were lost in melanomas. In cultured mother cells, the researchers saw that after loss of PTEN, the so-called senescense program (which causes the moles to go to sleep) became defective.

Progression to cancer

Then we could put the puzzle pieces in place. Mutation of the BRAF gene causes a birthmark. The PTEN tumor suppressor then ensures that the cells undergo senescence. But a second mutation, now in the PTEN gene, disables the senescence mechanism, so that birthmark cells start dividing again, according to Peeper. In the laboratory, the team was able to cause melanoma cells cultured with specific inhibitors to undergo senescence again.

Publication and further research

It cannot be ruled out that further mutations are required for the formation of melanoma. The researchers will therefore continue with the research. Facts may also emerge that could provide grounds for improving diagnostics.This research, which was partly financed by the Queen Wilhelmina Research Prize from KWF Cancer Control to these researchers and by NWO, was published on May 1 in the renowned scientific journal Genes & Development.