Nature. A study on the most common form of melanoma in Latin America, Africa and Asia warns about the lack of cancer genetics research in non-European populations

Carla Daniela Robles-Espinoza / Carla Daniela Robles-Espinoza.

Melanoma, the most aggressive form of skin cancer, is not always caused by sun exposure. In fact, the most common type of melanoma in several countries in Africa, Asia and Latin America is acral melanoma, which is not related to sunlight. But little research has been conducted into this form of cancer precisely because it represents a very low proportion of melanoma cases in people of European origin. A study in Nature addresses the genetics of acral melanoma in the Mexican population for the first time, providing information that could help better understand how to approach treatment in many cases.

The lead authors, from the National Autonomous University of Mexico (UNAM) working with the National Cancer Research Centre (CNIO), warn that Latin American populations are very underrepresented in cancer genomics research.

The majority of the samples are of European ancestry

Specifically, they estimate that only 1% of the samples in databases, essential for researching genes involved in cancer and their interaction with the environment, and for improving treatments, are from people of Latin American origin.

The problem affects non-European populations in general: “More than 80% of the samples in The Cancer Genome Atlas [an international project studying the genomic profiles of 30 types of cancer] were classified as having European ancestry,” noted a previous study by Carla Daniela Robles-Espinoza, the lead author of the study now published in Nature. The Pan-Cancer Analysis of Whole Genomes, another international collaboration, contains only 5% of samples of African ancestry.

According to Robles-Espinoza, in the aforementioned 2023 study, 70% of the cell lines commonly used in cancer research are of European descent, “although this is improving,” the researcher stated today.

Melanoma under the hands, feet and nails 

“To learn how to treat cancer in different populations, we need to genomically study patients of diverse ancestry and geographical origins,” explains Robles-Espinoza. Cancer originates and develops due to both genetic factors, which vary depending on the population, and environmental exposures, which also vary with geographical location; that’s why it’s very important to have patients from different backgrounds represented in databases.

The study in Nature highlights the low genetic diversity in global sample repositories, and the relative lack of studies on acral melanoma, the most frequently reported type of melanoma in some low- and middle-income countries.

Acral melanoma, like all types of melanoma, is a cancer of the melanocytes, the cells that produce the pigment that gives colour to the skin, eyes and hair. But while the most common melanoma in Europe appears in sun-exposed areas, such as the arms and legs, acral melanoma occurs on the soles of the feet, the palms of the hands and under the nails, and is not associated with sunlight.

The study in Nature reveals genetic alterations that are specific to acral melanoma. The authors studied melanomas from nearly a hundred Mexican patients and identified “the genes that were most frequently mutated, and the regions of the genome that showed alterations,” explained Robles-Espinoza.

Unique genetic alterations

They concluded that acral melanoma could originate in different types of melanocytes and that, as a result, the genetic alterations would be different. They found that patients of European descent were more likely to have a mutated BRAF gene, which is an important finding because there are treatments specifically targeted at this gene. 

“Other patients have different mutations, so they would not benefit from these therapies; they would need other strategies,” Robles-Espinoza points out.

The study was carried out in collaboration with the Digital Genomics Group at CNIO, which investigates the patterns of mutations that occur in DNA due to specific molecular processes and environmental exposures. In simple terms, each carcinogenic agent – such as tobacco or sun exposure – produces a unique set of mutations, like a fingerprint on the tumour’s genome.

Analysing these mutational signatures in Mexican samples of acral melanoma helped confirm that “they did not have traces of sun exposure in their genome. The mutational signatures associated with sunlight are very evident in cutaneous melanomas and in other tumours in sun-exposed areas, such as lip cancer,” explains Marcos Díaz Gay, head of the group at CNIO.

This researcher also points out that cancer research has historically been limited in terms of diversity of genetic ancestries and geographical origins. Díaz Gay says, “This makes the diagnosis and the development of better treatments for non-European population groups more difficult.”

About the National Cancer Research Centre (CNIO) The National Cancer Research Centre (CNIO) is a public research centre under the Department of Science, Innovation and Universities. It is the largest cancer research centre in Spain and one of the most important in Europe. It includes around five hundred scientists, along with support staff, who are working to improve the prevention, diagnosis and treatment of cancer.
 

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