P. Basurto-Lozada, Martha Estefania Vázquez‐Cruz, Christian Molina-Aguilar, Amanda Jiang, Dekker C. Deacon, Dennis Cerrato-Izaguirre, Irving Simonin-Wilmer, Fernanda Guadalupe Arriaga-González, Kenya L. Contreras-Ramírez, Emiliano Ferro-Rodríguez, Jamie Billington, Eric T. Dawson, J. Rene C. Wong-Ramirez, Johana Itzel Ramos-Galguera, Alethia Álvarez-Cano, Dorian Yarih García-Ortega, O. Isaac García-Salinas, Alfredo Hidalgo-Miranda, Mireya Cisneros-Villanueva, Peter A. Johansson, Héctor Martínez-Said, Pilar Gallego-García, Mark J Arends, Ingrid Ferreira, Mark Tullett, Rebeca Olvera-León, Louise van der Weyden, Martín del Castillo Velasco-Herrera, Rodrigo go Roldán-Marín, H. Vidaurri de la Cruz, Luis Alberto Tavares-de-la-Paz, Diego Hinojosa-Ugarte, Rachel L. Belote, D. Timothy Bishop, Marcos Díaz-Gay, Ludmil Alexandrov, Yesennia Sánchez-Pérez, Gino K. In, Richard M. White, Patrícia A. Possik, Robert L. Judson-Torres, David J. Adams, Carla Daniela Robles Espinoza
Abstract Acral melanoma, which is not ultraviolet-associated, is the type of melanoma reported most commonly in several non-European-descent populations 1–3 , including in Mexican people 4 . Latin American samples are substantially under-represented in global cancer genomics studies 5 , which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures 6–8 . 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 admixture 9 . 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.