Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma

Kim Wong, Louise van der Weyden, Courtney R. Schott, Alastair Foote, Fernando Constantino-Casas, Sionagh Smith, Jane M. Dobson, Elizabeth P Murchison, Hong Wu, Iwei Yeh, Douglas R. Fullen, Nancy Joseph, Boris Bastian , Rajiv M. Patel, Iñigo Martincorena, Carla Daniela Robles-Espinoza, Vivek Iyer, Marieke L. Kuijjer, Mark J. Arends, Thomas BrennPaul W. Harms, Geoffrey A. Wood, David J Adams

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. We performed a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data revealed recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. A UV mutation signature was identified in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identified several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggested pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.
Original languageEnglish
JournalNature Communications
Publication statusPublished - 21 Jan 2019


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