# Ancestry and somatic profile indicate acral melanoma origin and prognosis

## TL;DR

This study analyzes acral melanoma in Mexican patients to understand its origins and prognosis, emphasizing the need for diverse ancestry representation in cancer research.

## Contribution

The study provides new insights into acral melanoma's genetic and transcriptional profiles in a genetically admixed Mexican population.

## Key findings

- Fewer mutations in classical driver genes like BRAF, NRAS, or NF1 were found compared to other melanoma studies.
- Higher European ancestry in patients correlated with increased BRAF mutation frequency.
- Transcriptional profiling identified three expression clusters associated with survival outcomes.

## Abstract

Acral melanoma, which is not ultraviolet-associated, is the type of melanoma reported most commonly in several non-European-descent populations1–3, including in Mexican people4. Latin American samples are substantially under-represented in global cancer genomics studies5, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures6–8. To address this, we characterized the genome and transcriptome of 123 acral melanoma tumours from 92 Mexican patients—a population notable because of its genetic admixture9. Compared with other studies of melanoma, we found fewer mutations in classical driver genes such as BRAF, NRAS or NF1. Although most patients had predominantly Amerindian genetic ancestry, those with higher European ancestry had increased frequency of BRAF mutations. The tumours with activating BRAF mutations had a transcriptional profile more similar to cutaneous non-volar melanocytes, indicating that acral melanomas in these patients may arise from a distinct cell of origin compared with other tumours arising in these locations. Transcriptional profiling defined three expression clusters; these characteristics were associated with recurrence-free and overall survival. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.