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Nat Commun. 2019 Jan 21;10(1):353. doi: 10.1038/s41467-018-08081-1.

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

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Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Department of Pathobiology, University of Guelph, 50 Stone Road E., Guelph, ON, N1G 2W1, Canada.
Rossdales Equine Hospital and Diagnostic Centre, High Street, Newmarket, Suffolk, CB8 8JS, UK.
Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, CB3 0ES, UK.
The Royal (Dick) School of Veterinary Studies and The Roslin Institute, Easter Bush Campus, Midlothian, EH25 9RG, UK.
Departments of Dermatology and Pathology, University of California, San Francisco, CA, 94143, USA.
Departments of Pathology and Dermatology, University of Michigan Medical School, 3261 Medical Science I, 1301 Catherine, Ann Arbor, MI, 48109-5602, USA.
Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Blvd Juriquilla 3001, Santiago de Querétaro, 76230, Mexico.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, University of Oslo, 0349, Oslo, Norway.
University of Edinburgh, Division of Pathology, Centre for Comparative Pathology, Cancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK.
Department of Pathology and Laboratory Medicine, Cumming School of Medicine and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, T2L 2K8, Canada.
Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.


Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform 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 reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature 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 identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests 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.

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