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Evaluation of variants of melanoma-associated antigen genes and mRNA transcripts in melanomas of dogs

Anneliese J. Stell BVM&S, PhD1, Jane M. Dobson BVetMed, DVetMed2, Timothy J. Scase BVM&S, PhD3, and Brian Catchpole BVetMed, PhD4
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  • 1 Departments of Veterinary Clinical Science and Pathology and Infectious Diseases, Royal Veterinary College, North Mymms, Hatfield, Hertfordshire, AL9 7TA, England.
  • | 2 Department of Veterinary Medicine, Cambridge Veterinary School, University of Cambridge, Cambridge, Cambridgeshire, CB3 OES, England.
  • | 3 Bridge Pathology Ltd, Courtyard House, 26 Oakfield Rd, Bristol, Avon, BS8 2AT, England.
  • | 4 Departments of Veterinary Clinical Science and Pathology and Infectious Diseases, Royal Veterinary College, North Mymms, Hatfield, Hertfordshire, AL9 7TA, England.

Abstract

Objective—To characterize variability in melanoma-associated antigen (MAA) genes and gene expression in melanomas of dogs.

Animals—18 dogs with malignant melanomas and 8 healthy control dogs.

Procedures—cDNA was prepared from malignant melanoma biopsy specimens and from pigmented oral mucocutaneous tissues of healthy control dogs. Genomic DNA was extracted from poorly pigmented melanomas. A PCR assay was performed by use of Melan-A, SILV, or tyrosinase-specific primers.

Results—Splice variants of Melan-A and SILV were identified in malignant melanomas and also in healthy pigmented tissues, whereas a tyrosinase splice variant was detected in melanoma tissues only. A short interspersed nuclear element (SINE) insertion mutation was identified in the SILV gene in 1 of 10 poorly pigmented melanomas. Six novel exonic single nucleotide polymorphisms (SNPs; 3 synonymous and 3 nonsynonymous) were detected in the tyrosinase gene, and 1 nonsynonymous exonic SNP was detected in the SILV gene.

Conclusions and Clinical Relevance—Variants of MAA mRNA were detected in malignant melanoma tissues of dogs. The importance of MAA alternative transcripts expressed in melanomas and normal pigmented tissues was unclear, but they may have represented a means of regulating melanin synthesis. The tyrosinase splice variant was detected only in melanomas and could potentially be a tumor-specific target for immunotherapy. A SILV SINE insertion mutation was identified in a melanoma from a Great Dane, a breed known to carry this mutation (associated with merle coat color). The nonsynonymous SNPs detected in tyrosinase and SILV transcripts did not appear to affect tumor pigmentation.

Contributor Notes

Supported by Merial Animal Health, Wellcome Trust (equipment grant No. 068969), and the Cadogan Fellowship in Veterinary Oncology from the Royal Veterinary College.

Presented in abstract form at the Association for Veterinary Teaching and Research Work Annual Scientific Conference, Scarborough, England, April 2004; 24th Veterinary Cancer Society Conference, Kansas City, Mo, November 2004; and European College of Veterinary Internal Medicine-Companion Animals Congress, Glasgow, Scotland, September 2005.

Address correspondence to Dr. Stell (astell@rvc.ac.uk).