A genetic study of Mexican patients with acral melanoma revealed that the cancer subtype encompasses three groups that may each have distinct gene expressions associated with different survival outcomes, according to findings published in Nature.
“We found that acral melanoma is not a single disease. Tumors fall into distinct biological groups that are linked to different patient outcomes,” said first study author Patricia Basurto-Lozada, a PhD student in the Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Santiago de Querétaro, Mexico. “This information may be crucial for developing targeted treatments for acral melanoma in the future and ultimately improving the lives of patients.”
Background and Study Methods
In Mexican people, acral melanoma is the most common form of melanoma. Acral melanoma is influenced by ancestry as well as environmental exposures.
Researchers explored the genome and transcriptome of 123 samples of acral melanoma tumors from 92 Mexican patients. This was one of the largest cohorts ever reported for analyzing this tumor type.
Key Findings
In this population, acral melanoma samples were associated with fewer mutations in standard driver genes. Those with more European ancestry had more BRAF mutations, and activating BRAF mutations were associated with a unique transcriptional profile that is more in line with that of cutaneous nonvolar melanocytes.
Overall, three expression clusters were associated with different recurrence-free survival and overall survival outcomes. Samples in which there were more immune-related genes were associated with improved outcomes; these patients also had more favorable clinical characteristics, such as earlier stages at diagnosis and lower mitotic indexes. The second cluster group had a more proliferative gene signature and expressed more pigmentation genes; these patients showed the worst survival. Tumors that expressed variations in their metabolic pathway were associated with more variable outcomes.
The study authors added that the study shows the value of studying diverse populations to gain a better understanding of tumor evolution.
“Our research highlights the underrepresented nature of cancer genomics studies. By emphasizing the need for more diversity in research and clinical trials, we hope the findings contribute to improved outcomes for patients with rare and aggressive cancers like acral melanoma,” stated co-senior author, David J. Adams, MD, FRCP, FMedSci, Interim Head of the Somatic Genomic Programme and Senior Group Leader, Wellcome Sanger Institute in Hinxton, United Kingdom.
DISCLOSURE: Funding for this research was supported in part by Wellcome Sanger Institute, the Melanoma Research Alliance, the Mexican National Council of Humainities, and more. For full disclosures of the study authors, visit nature.com.
