Study locates driver for melanoma

ENVIRO FACTORS HAVE LARGER ROLE

Harmless moles and cancerous melanomas are more similar than you might think: they’re both skin tumours, and they’re both formed from the same kind of cell. But one simply sits on your skin, while the other is the most serious form of skin cancer. At what point does the benign become dangerous, and what can be done to prevent it?

New research from the Huntsman Cancer Institute at the University of Utah show that environmental factors have a bigger impact than previously believed. The findings can help people understand how to prevent moles from turning into melanomas. “We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes become melanomas,” Dr. Robert Judson-torres, one of the study’s authors, told the centre’s news outlet.

Most moles and many melanomas (75 per cent and 50 per cent, respectively) occur when there are changes activated in melanocytes, the cells that darken the skin to protect it from the sun. These changes are called BRAF gene mutations, and they also occur in other kinds of illnesses, including cancer of the lung and colon.

The study, published in the journal elife Sciences, wanted to understand what, besides the presence of these multiple gene mutations, causes melanoma. Before the Huntsman study, it was understood that having just one of these mutations — the BRAFV600E mutation, to be specific — stopped the cell from dividing, which resulted in a mole. It’s when the BRAFV600E mutation is present with other mutations that melanoma occurs, because the cells continue to divide uncontrollably.

“A number of studies have challenged this model in recent years,” Judson-torres said. “These studies have provided excellent data ... but what they have all lacked is an alternative explanation, which has remained elusive.”

The research team looked at moles and melanomas using transcriptomic profiling, which helps them see molecular differences between moles and melanomas, and digital holographic cytometry, which tracks changes in human cells. They discovered that additional gene mutations aren’t the only way these skin cells turn into melanoma. The melanocytes are also impacted by environmental signals, which indicate to them whether they should divide uncontrollably (causing melanoma) or simply stop dividing (causing a benign mole). They express genes in different environments, Judson-torres explained.

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

Melanoma is distressingly common, and is on the rise — especially in women under 40. In the 1930s, it affected about one in 1,500 people, according to the Melanoma Network of Canada — less than 100 years later, that number has ballooned to one in 63 people.