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- Title
Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma.
- Authors
Wong, Kim; van der Weyden, Louise; Schott, Courtney R.; Foote, Alastair; Constantino-Casas, Fernando; Smith, Sionagh; Dobson, Jane M.; Murchison, Elizabeth P.; Wu, Hong; Yeh, Iwei; Fullen, Douglas R.; Joseph, Nancy; Bastian, Boris C.; Patel, Rajiv M.; Martincorena, Inigo; Robles-Espinoza, Carla Daniela; Iyer, Vivek; Kuijjer, Marieke L.; Arends, Mark J.; Brenn, Thomas
- Abstract
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. Mucosal melanoma is a rare melanoma subtype that is poorly characterised. Here, the authors sequenced human, canine, and equine melanoma samples and performed a cross-species analysis, which revealed candidate driver genes, recurrent copy number alterations in regions syntenic between species, extensive intra-tumour heterogeneity and potential germline predisposing alleles
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-08081-1