A study of Mexican patients reveals previously unknown details about acral melanoma, the most common subtype of skin cancer in Latin America.

For decades, acral melanoma, an aggressive skin cancer that appears on the palms of the hands, soles of the feet, or under the nails, has been considered rare in medical literature due to its low incidence in the United States and Europe. However, it is the most common type of melanoma in Latin America: in Mexico, this cancer, for which there is no specific treatment, accounts for half of the 3,500 annual melanoma diagnoses, most of which are in advanced stages due to the atypical location of the lesions and their silent growth. This was the scenario that led Daniela Robles-Espinoza, coordinator of the International Laboratory for Human Genome Research (LIIGH) at UNAM, to embark on a long-term investigation into the genetic mysteries behind acral melanoma in 2015. The result, a pioneering study conducted with samples from Mexican patients, reveals unprecedented details about the genes and mutations responsible for this cancer and lays the foundation for the development of effective treatments. Melanoma originates when melanocytes—a type of cell that produces the skin's natural pigment—undergo genetic mutations and multiply uncontrollably. Unlike other skin cancers, acral melanoma is not linked to ultraviolet radiation and therefore does not appear on areas of the body most exposed to sunlight. Instead, lesions appear as asymmetrical moles with irregular edges and more than one shade. "Delays in diagnosis are often associated with their atypical location and initial misdiagnosis. Most patients have previously consulted several doctors and received treatment for other conditions," Héctor Martínez Said, an oncologist and deputy director of surgery at the National Cancer Institute, whose participation in the study was key to moving from clinical medicine to genomic analysis, explained to EL PAÍS. Currently, acral melanoma is treated similarly to other types of skin cancer, despite having characteristics that make it unique. The study published in Nature reveals that a person's genetic origin directly influences the type of mutations their cancer develops. “As the Mexican population is mixed, we have different proportions of different ancestries, mainly Amerindian, European, and African,” says Patricia Basurto, first author of the study. The research showed that patients with a higher proportion of European ancestry more frequently present mutations in the BRAF gene, a key gene in other cancers that has been better studied and for which specific therapies exist. In contrast, patients with a high degree of Native American ancestry (the common denominator in most Mexicans) tend to develop mutations in other genes that have not yet been thoroughly investigated, a factor that explains why some current therapies for acral melanoma are less effective in Latin American patients. The article also suggests that, contrary to what was previously believed, acral melanoma tumors can originate from two different types of melanocytes, a factor that may be decisive in the development of effective therapies. “We know that different cell types respond better to different treatments, and knowing the cellular origin of certain tumors could help us find treatment strategies,” says Robles-Espinoza. Genomic studies are key to understanding in detail how each type of cancer evolves and identifying the specific mutations that cause its replication. "Studying the genetics of tumors can not only teach us how they evolve, but also which genes are being affected and generate drugs specifically targeted against the effect of those mutations," explains Basurto, citing advances in cutaneous melanoma—the most studied type of melanoma—and how the discovery of a mutation common in more than half of tumors made it possible to develop specially targeted treatments with very good results. “This is a key project for understanding the biological and clinical differences between acral melanoma and other subtypes of melanoma, which are precisely those for which current therapies have been developed,” adds Martínez Said. The research, the result of a collaboration between UNAM, the National Cancer Institute, the National Institute of Genomic Medicine, and other organizations in Brazil and England, contributes to our understanding of how cancer develops in the Mexican population. Robles-Espinoza defines it as “an atlas of a little-studied cancer in a little-studied population, something that is very rare.” The results also highlight the representativeness gap in global clinical research, a bias present in studies, trials, and tests that concentrates samples in populations from regions with established research networks, such as Europe and the United States, and excludes data from groups such as Latin Americans, Africans, or Asians. “Virtually all studies on this type of cancer were conducted in European populations, and there was a gap in research that could have implications for treatment to help learn more about this disease in Mexicans,” argues Robles-Espinoza, while calling for a boost to collaborative science in the region: "We must close the gap in clinical research in this country and in Latin America. It is difficult for many reasons, but we must work together to study our populations and develop therapies that are useful here, that have an impact on patients here.