Study maps changes that make melanoma more serious, could lead to improved therapy and diagnosis

A group of researchers from Brazil and France managed to identify markers left by sunlight in the genomes of people suffering from skin melanoma. The research article was published in Communications of nature also offers new insights into other melanomas not caused by exposure to ultraviolet (UV) radiation.

“We discovered that some changes are markers for the patient’s survival. We were able to predict whether a person would have a greater or lesser chance of survival thanks to these markers present in their DNA,” said Anna Luisa Silva Almeida Vicente, first author of the article. .

Vicente performed part of the analysis during a research internship at the International Agency for Research on Cancer (IARC) in Lyon, France.

A study involving IARC-affiliated researchers has identified molecular characteristics that can indicate aggressiveness and guide treatment.

One of the melanomas analyzed was cutaneous melanoma, which has one subtype associated with solar radiation and another not associated with UV radiation. These tumors occur primarily in white people and mainly affect parts of the skin that are exposed to the sun’s rays.

A small number of samples come from acral melanoma, which is unrelated to UV exposure, is the most common type in dark-skinned people, and forms on the palms and soles and under the nails. Little research has been done on acral melanoma. Most studies have focused on European and US populations.

“There are several subtypes of melanoma. All of them can be aggressive, but aggressiveness is more common in some. There are histological characteristics that are determined under the microscope and genetic features, some of which are known and used for treatment. We are rediscovering a new path in this field, which is epigenetic and takes into account the presence of exposure to sunlight that causes changes not in the DNA sequence [i.e. genetic mutations]but from how it is expressed and encodes proteins that are important for the normal functioning of the body,” said Vinicius de Lima Vazquez, executive director of the Hospital de Amor Institute for Education and Research and penultimate author of the paper.

Molecular information

Epigenetic changes are caused by environmental factors. They are reversible and do not change the DNA sequence to cause mutations, but they can change the way the body reads it, and they can be inherited.

In the study, the researchers used several techniques to analyze DNA methylation, an epigenetic change that involves a biochemical change in which the action of enzymes adds methyl groups to a DNA molecule.

DNA methylation is a necessary process, but can cause cellular dysfunction and lead to cancer if it is disrupted by external factors such as excessive exposure to UV light.

The researchers analyzed 112 cutaneous melanoma samples and 21 acral melanoma samples. The first were collected from the Hospital de Amor and an international database that mainly represents European and American patients. All acral melanoma specimens came from Barretos Hospital.

Analysis of methylated DNA showed that cutaneous melanomas not associated with sunlight exposure are much more similar to acral melanomas (which are not affected by UV radiation and are more common in dark-skinned people) than to cutaneous melanomas associated with excessive UV exposure . .

These results were supported by survival rates that were lower in patients with acral and cutaneous melanoma not associated with sunlight exposure than in patients with cutaneous melanoma associated with UV exposure.

“We concluded that these two non-sun-related tumors can be histologically classified as different subtypes, but are molecularly very similar in terms of methylation and also have a lower survival rate. This is an important part of the study and can be clinical in nature. impact in the future,” said Vicente, who is currently pursuing a PhD at the University of California, San Francisco (UCSF) in the US.

Another finding that caught the researchers’ attention was that mutations in the BRAF, NRAS, and NF1 genes were not seen in most acral melanomas, although they are common in cutaneous melanomas.

Moreover, 28.6% of patients with acral melanoma were black, while only 5.6% with cutaneous melanoma melanoma samples from Hospital de Amor were from patients with dark skin.

Some treatments for other types of cancer are moving toward associating molecular information with prognosis and identifying patients who respond better to available treatments, Vasquez said. This is one of the goals of studying skin tumors.

“More information like this about melanomas is needed for use in everyday medicine. Such studies point to new areas of research to be explored and pave the way for more personalized treatment,” he said.