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

Author

Listed:
  • Kim Wong

    (Wellcome Trust Genome Campus)

  • Louise van der Weyden

    (Wellcome Trust Genome Campus)

  • Courtney R. Schott

    (University of Guelph)

  • Alastair Foote

    (High Street)

  • Fernando Constantino-Casas

    (University of Cambridge)

  • Sionagh Smith

    (Easter Bush Campus)

  • Jane M. Dobson

    (University of Cambridge)

  • Elizabeth P. Murchison

    (University of Cambridge)

  • Hong Wu

    (University of California)

  • Iwei Yeh

    (University of California)

  • Douglas R. Fullen

    (University of Michigan Medical School)

  • Nancy Joseph

    (University of California)

  • Boris C. Bastian

    (University of California)

  • Rajiv M. Patel

    (University of Michigan Medical School)

  • Inigo Martincorena

    (Wellcome Trust Genome Campus)

  • Carla Daniela Robles-Espinoza

    (Wellcome Trust Genome Campus
    Universidad Nacional Autónoma de México, Campus Juriquilla)

  • Vivek Iyer

    (Wellcome Trust Genome Campus)

  • Marieke L. Kuijjer

    (Harvard T.H. Chan School of Public Health
    Dana-Farber Cancer Institute
    Faculty of Medicine, University of Oslo)

  • Mark J. Arends

    (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)

  • Thomas Brenn

    (Wellcome Trust Genome Campus
    University of Calgary)

  • Paul W. Harms

    (University of Michigan Medical School)

  • Geoffrey A. Wood

    (University of Guelph)

  • David J. Adams

    (Wellcome Trust Genome Campus)

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.

Suggested Citation

  • 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 &, 2019. "Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08081-1
    DOI: 10.1038/s41467-018-08081-1
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    Cited by:

    1. Khalid AbdulJabbar & Simon P. Castillo & Katherine Hughes & Hannah Davidson & Amy M. Boddy & Lisa M. Abegglen & Lucia Minoli & Selina Iussich & Elizabeth P. Murchison & Trevor A. Graham & Simon Spiro , 2023. "Bridging clinic and wildlife care with AI-powered pan-species computational pathology," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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