Markers left by exposure to sunlight were found in the genomes of cutaneous melanoma patients

A team of researchers in Brazil and France succeeded in finding markers
left by exposure to sunlight in the genomes of cutaneous melanoma patients.
An article about this research, published in Nature Communications, also provides new insights
into other melanoma that are not caused by ultraviolet radiation.

"We found that some changes were markers
of patient survival.
We were able to predict whether a person was more likely to survive thanks to these markers present in their DNA," said
Anna Luiza Silva Almeida Vicente, first author of the paper.
The study was carried out during her doctoral studies at the Hospital de Amor, located at the Baretos Cancer Hospital
in Såo Paulo (Brazil).

Vicente conducted part of the analysis during a research internship at the International Agency for Research on Cancer (IARC) in Lyon, France, and was awarded a FAPESP fellowship
.

IARC researchers participated in the study, revealing molecular signatures
that may indicate aggression and guide treatment.

One of the melanoma analyzed was cutaneous melanoma, which has one subtype associated with solar radiation and the other unrelated
to ultraviolet light.
These tumors occur mainly in white people and mainly affect parts of the skin
exposed to sunlight.

A small percentage of the sample came from acral melanoma, which is not associated with ultraviolet light and is the most common type in darker-skinned people, forming on the palms, soles of the feet, and under the
nails.
There is little
research on acral melanoma.
Most studies have focused on populations
in Europe and the United States.

"There are several subtypes of
melanoma.
They all have aggression, but aggression is more common
in some animals.
There are histological features, which are determined under the microscope, and genetic features, some of which are known and used to guide treatment
.
We are opening up a new pathway in this field, which is epigenetic, considering that the alteration caused by sunlight exposure is not the DNA sequence (i.
e.
genetic mutation), but the way it expresses and encodes proteins that are important for the normal functioning of the organism," said
Vinicius de Lima Vazquez, executive director of the Institute of Education at Amor Hospital and penultimate author of the article.

Information for molecules

Epigenetic changes are due to environmental factors
.
They are reversible and do not change the DNA sequence to cause mutations, but they can change the way the body reads
DNA, and they may be heritable.

In this study, the researchers used several techniques to analyze DNA methylation, an epigenetic alteration that involves the action of enzymes to increase the biochemical changes
in DNA molecules to methyl groups.

DNA methylation is a necessary process, but if due to external factors, such as excessive exposure to ultraviolet light, methylation can lead to cell dysfunction and lead to cancer
.

The researchers analyzed 112 cutaneous melanoma samples and 21 acral melanoma samples
.
The former comes from Love Hospital and an international database
that mainly represents European and American patients.
All acral melanoma samples came from Baretos Hospital
.

Methylation DNA analysis showed that cutaneous melanomas, associated with excessive exposure to ultraviolet light, were more similar
to acral melanoma (acral melanoma is not affected by ultraviolet radiation and is more common in dark-skinned people).

These findings are confirmed by survival rates, with patients with acral and cutaneous melanoma having lower survival rates than cutaneous melanoma patients with exposure to ultraviolet light
.

"We concluded that these two tumors unrelated to sun exposure can be histologically classified into different subtypes, but from a methylation perspective, they are very similar in molecule and have lower
survival rates.
" It's an important part of research that could have clinical implications in the future," said Vicente, who is currently conducting postdoctoral research
at the University of California, San Francisco (UCSF).

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

In addition, 28.
6% of acral melanoma patients were black, while only 5.
6% of cutaneous melanoma samples came from dark-skinned patients
.

According to Vázquez, some treatments for other types of cancer are moving
toward linking molecular information to prognosis and determining which patients respond better to existing therapies.
This is one of the goals of
skin tumor research.

"More information
about melanoma is needed in everyday medicine.
Studies like this point to new directions of investigation and pave the way
for more personalized treatments.
”