title: Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.
abstract: Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model.
authors.affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Simpson
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
authors.forename: Helen T
authors.initials: HT
authors.lastname: Michael
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Webster
authors.forename: Manju L
authors.initials: ML
authors.lastname: Prasad
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Conway
authors.forename: Victor M
authors.initials: VM
authors.lastname: Prieto
authors.forename: Joy M
authors.initials: JM
authors.lastname: Gary
authors.forename: Michael H
authors.initials: MH
authors.lastname: Goldschmidt
authors.forename: D Glen
authors.initials: DG
authors.lastname: Esplin
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Smedley
authors.forename: Adriano
authors.initials: A
authors.lastname: Piris
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Meuten
authors.forename: Matti
authors.initials: M
authors.lastname: Kiupel
authors.forename: Chyi-Chia R
authors.initials: CC
authors.lastname: Lee
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Ward
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Dwyer
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Davis
authors.forename: Miriam R
authors.initials: MR
authors.lastname: Anver
authors.forename: Alfredo A
authors.initials: AA
authors.lastname: Molinolo
authors.forename: Shelley B
authors.initials: SB
authors.lastname: Hoover
authors.forename: Jaime
authors.initials: J
authors.lastname: Rodriguez-Canales
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary
chemical_list: D009363:Neoplasm Proteins
keywords: animal model; clinical trial design; comparative study; digital telepathology; image analysis; melanoma; signal transduction