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Nature communications2019; 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.

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.
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Publication Date: 2019-01-21 PubMed ID: 30664638PubMed Central: PMC6341101DOI: 10.1038/s41467-018-08081-1Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study explores the genetic make-up of a rare subtype of human melanoma called mucosal melanoma by comparing its genomic landscape with that of similar types of melanoma found in dogs and horses.

Background

  • Mucosal melanoma is a type of skin cancer that is not well understood due to its rarity.
  • This study aims to gain insights into this disease by comparing its genetic profile with similar diseases found in dogs and horses.

Method

  • To compare the genomic landscape, the research team sequenced the genes of tumor-germline pairs from 46 human, 65 canine, and 28 equine primary melanoma cases.
  • This allowed the researchers to pinpoint recurrently mutated driver genes that are common between species, as well as identify pathogenic germline alleles.

Findings

  • Commonly mutated genes included NRAS, FAT4, PTPRJ, TP53, and PTEN.
  • Pathogenic germline alleles found included those of BRCA1, BRCA2, and TP53.
  • A UV mutation signature was detected in a small subset of samples, including those from human cases on the lip and nasal mucosa.
  • In analyzing recurrent copy number alterations, several candidate driver genes, such as MDM2, B2M, KNSTRN, and BUB1B, were identified.
  • Comparison of somatic mutations in recurrences and metastases with those in primary tumors suggested that pervasive intra-tumor heterogeneity is common.

Significance

  • The findings of this study suggest that there are some genetic overlaps in mucosal melanomas across different species.
  • However, there appear to also be unique paths to tumorigenesis for each species.
  • This research enhances our understanding of mucosal melanoma, potentially opening up new pathways for targeted treatment strategies for this rare form of skin cancer.

Cite This Article

APA
Wong K, van der Weyden L, Schott CR, Foote A, Constantino-Casas F, Smith S, Dobson JM, Murchison EP, Wu H, Yeh I, Fullen DR, Joseph N, Bastian BC, Patel RM, Martincorena I, Robles-Espinoza CD, Iyer V, Kuijjer ML, Arends MJ, Brenn T, Harms PW, Wood GA, Adams DJ. (2019). Cross-species genomic landscape comparison of human mucosal melanoma with canine oral and equine melanoma. Nat Commun, 10(1), 353. https://doi.org/10.1038/s41467-018-08081-1

Publication

Nature communications
ISSN: 2041-1723
NlmUniqueID: 101528555
Country: England
Language: English
Volume: 10
Issue: 1
Pages: 353

Researcher Affiliations

Wong, Kim
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
van der Weyden, Louise
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Schott, Courtney R
  • Department of Pathobiology, University of Guelph, 50 Stone Road E., Guelph, ON, N1G 2W1, Canada.
Foote, Alastair
  • Rossdales Equine Hospital and Diagnostic Centre, High Street, Newmarket, Suffolk, CB8 8JS, UK.
Constantino-Casas, Fernando
  • Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, CB3 0ES, UK.
Smith, Sionagh
  • The Royal (Dick) School of Veterinary Studies and The Roslin Institute, Easter Bush Campus, Midlothian, EH25 9RG, UK.
Dobson, Jane M
  • Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, CB3 0ES, UK.
Murchison, Elizabeth P
  • Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, CB3 0ES, UK.
Wu, Hong
  • Departments of Dermatology and Pathology, University of California, San Francisco, CA, 94143, USA.
Yeh, Iwei
  • Departments of Dermatology and Pathology, University of California, San Francisco, CA, 94143, USA.
Fullen, Douglas R
  • Departments of Pathology and Dermatology, University of Michigan Medical School, 3261 Medical Science I, 1301 Catherine, Ann Arbor, MI, 48109-5602, USA.
Joseph, Nancy
  • Departments of Dermatology and Pathology, University of California, San Francisco, CA, 94143, USA.
Bastian, Boris C
  • Departments of Dermatology and Pathology, University of California, San Francisco, CA, 94143, USA.
Patel, Rajiv M
  • Departments of Pathology and Dermatology, University of Michigan Medical School, 3261 Medical Science I, 1301 Catherine, Ann Arbor, MI, 48109-5602, USA.
Martincorena, Inigo
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Robles-Espinoza, Carla Daniela
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Blvd Juriquilla 3001, Santiago de Querétaro, 76230, Mexico.
Iyer, Vivek
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
Kuijjer, Marieke L
  • 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.
Arends, Mark J
  • 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.
Brenn, Thomas
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Department of Pathology and Laboratory Medicine, Cumming School of Medicine and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, T2L 2K8, Canada.
Harms, Paul W
  • Departments of Pathology and Dermatology, University of Michigan Medical School, 3261 Medical Science I, 1301 Catherine, Ann Arbor, MI, 48109-5602, USA.
Wood, Geoffrey A
  • Department of Pathobiology, University of Guelph, 50 Stone Road E., Guelph, ON, N1G 2W1, Canada.
Adams, David J
  • Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. da1@sanger.ac.uk.

MeSH Terms

  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Copy Number Variations
  • Dogs
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Germ-Line Mutation
  • Horses
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Recurrence, Local
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3 / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Species Specificity
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Grant Funding

  • Wellcome Trust
  • 21717 / Cancer Research UK
  • 21777 / Cancer Research UK
  • MR/S01473X/1 / Medical Research Council

Conflict of Interest Statement

The authors declare no competing interests.

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