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 C Bastian; Rajiv M Patel; Inigo Martincorena; Carla Daniela Robles-Espinoza; Vivek Iyer; Marieke L Kuijjer; Mark J Arends; Thomas Brenn; Paul W Harms; Geoffrey A Wood; David J Adams

doi:10.1038/s41467-018-08081-1

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

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

Authors

Kim Wong¹, Louise van der Weyden¹, Courtney R Schott², Alastair Foote³, Fernando Constantino-Casas⁴, Sionagh Smith⁵, Jane M Dobson⁴, Elizabeth P Murchison⁴, Hong Wu⁶, Iwei Yeh⁶, Douglas R Fullen⁷, Nancy Joseph⁶, Boris C Bastian⁶, Rajiv M Patel⁷, Inigo Martincorena¹, Carla Daniela Robles-Espinoza^{1

8}, Vivek Iyer¹, Marieke L Kuijjer^{9

10

11}, Mark J Arends¹², Thomas Brenn^{1

13}, Paul W Harms⁷, Geoffrey A Wood², David J Adams¹⁴

Affiliations

¹ Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
² Department of Pathobiology, University of Guelph, 50 Stone Road E., Guelph, ON, N1G 2W1, Canada.
³ Rossdales Equine Hospital and Diagnostic Centre, High Street, Newmarket, Suffolk, CB8 8JS, UK.
⁴ Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, CB3 0ES, UK.
⁵ The Royal (Dick) School of Veterinary Studies and The Roslin Institute, Easter Bush Campus, Midlothian, EH25 9RG, UK.
⁶ Departments of Dermatology and Pathology, University of California, San Francisco, CA, 94143, USA.
⁷ Departments of Pathology and Dermatology, University of Michigan Medical School, 3261 Medical Science I, 1301 Catherine, Ann Arbor, MI, 48109-5602, USA.
⁸ Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Blvd Juriquilla 3001, Santiago de Querétaro, 76230, Mexico.
⁹ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA.
¹⁰ Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
¹¹ Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, Faculty of Medicine, University of Oslo, 0349, Oslo, Norway.
¹² 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.
¹³ Department of Pathology and Laboratory Medicine, Cumming School of Medicine and Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, T2L 2K8, Canada.
¹⁴ Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. da1@sanger.ac.uk.

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

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

Substances

BRCA1 Protein
BRCA1 protein, human
BRCA2 Protein
BRCA2 protein, human
BUB1B protein, human
Cadherins
Cell Cycle Proteins
FAT4 protein, human
KNSTRN protein, human
Membrane Proteins
Microtubule-Associated Proteins
Neoplasm Proteins
TP53 protein, human
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2
Protein Serine-Threonine Kinases
PTPRJ protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 3
PTEN Phosphohydrolase
PTEN protein, human
GTP Phosphohydrolases
NRAS protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding