Study maps DNA changes that make melanoma more severe

A group of researchers from Brazil and France managed to unravel the marks that sun exposure leaves on the genome of people affected by cutaneous melanoma. The work, published in the journal Nature Communications, also brings a new understanding of what happens in other melanomas that are not caused by the effects of ultraviolet rays.

“We saw that some of these alterations are markers of patient survival. We were able to predict whether a person is more or less likely to survive thanks to these marks present in the DNA”, says Anna Luiza Silva Almeida Vicente, first author of the study conducted during her doctorate at the Hospital de Amor (formerly called Hospital do Câncer de Barretos).

Vicente carried out part of the analysis during a research internship at the International Agency for Research on Cancer (IARC), in France, with the support of a grant from Fapesp.

The study, which had the participation of researchers from the French institution, revealed the molecular characteristics that may indicate greater aggressiveness and guide the treatment.

One of the melanomas analyzed was cutaneous, which has a subtype linked to exposure to sunlight and another that is not related to ultraviolet radiation. These tumors mainly affect white individuals, mainly affecting parts of the skin exposed to the sun.

A smaller proportion of the samples were of acral melanoma, which is unrelated to exposure to ultraviolet rays, is more common in black individuals and occurs in parts of the body such as the palm of the hand and the sole of the foot. This type of melanoma is still largely neglected in research, usually focused on populations in Europe and the United States.

“There are several subtypes of melanoma and all can be aggressive, but in some this is more common. There are histological characterizations, that is, those that can be done under the microscope, and other genetic ones, some known and used to guide the treatment. new path in this area, that of epigenetics, taking into account the presence of exposure to the sun, which indicates alterations not in the DNA sequence [como são as mutações genéticas]but in the way it expresses itself and encodes proteins that are important for the normal functioning of the organism”, explains Vinicius de Lima Vazquez, executive director of the Teaching and Research Institute of Hospital de Amor and one of the study coordinators.

molecular information

Epigenetics is a field that studies how environmental factors affect the functions of the organism without changes in the DNA sequence (mutations). In the study, the researchers used different techniques to analyze the epigenetic change known as DNA methylation (a biochemical modification that involves the addition of a methyl group to the molecule through the action of enzymes).

DNA methylation is a necessary process for the body to function, but when unregulated by external factors — such as excessive exposure to ultraviolet rays, in the case of melanoma — it can cause cell dysfunction and lead to cancer.

The researchers analyzed a total of 112 samples of cutaneous melanoma and 21 of acral melanoma. In the first case, samples collected at the Hospital de Amor and from an international database were used, mainly from the United States and Europe. The acral melanomas were all from patients at the Barretos institution.

Analysis of the set of methylated DNA molecules showed that cutaneous melanomas unrelated to sun exposure are much more similar to acral melanomas — those that are also not influenced by ultraviolet rays and are more present in black people — than to linked cutaneous melanomas. to excess ultraviolet radiation.

The results are supported by the survival rates: acral and cutaneous melanomas not linked to sun exposure have a lower survival rate than cutaneous melanomas related to exposure to ultraviolet rays.

“We saw that these two tumors not linked to sun exposure can be classified by histology as being of different subtypes, but, from the point of view of methylation, they are molecularly very similar, including a shorter survival. This is an important aspect brought by the work and that may have a clinical impact in the future”, says Vicente, who is currently doing a postdoctoral work at the University of California San Francisco, in the United States.

Another result that caught the attention of the researchers was that the mutation in the genes BRAF, NRAS and NF1common in cutaneous melanomas, was not observed in most acral melanomas.

In addition, 28.6% of patients with acral melanoma were black. While in the cutaneous melanoma samples from Hospital de Amor, only 5.6% had the pigmented skin phenotype.

According to Vazquez, some treatments for other types of cancer are advancing in the sense of associating molecular information with the prognosis and of identifying the most responsive patients to available therapies. This is one of the goals in studies on skin tumors.

“Melanomas still lack information of this type that can be used on a daily basis. Studies like this bring new lines of investigation to be explored and pave the way for patients to be treated in an increasingly personalized way”, concludes the researcher. .