Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression

Blacklock, Kelly L. Bowlt; Birand, Zeynap; Selmic, Laura E.; Nelissen, Paulien; Murphy, Sue; Blackwood, Laura; Bass, Joyce; McKay, Jenny; Fox, Richard J.; Beaver, Stuart; Starkey, Mike

doi:10.1038/s41598-019-42839-x

Cited by 20 publications

(19 citation statements)

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“…[35][36][37][38] The expression of CXCR4 has only been studied in few canine cancer cell types such as oral melanoma, osteosarcoma, and hemangiosarcoma. [39][40][41] Future study to evaluate the expression of Iatrogenic hypothyroidism in dogs has been previously documented in patients which underwent surgery and radiation therapy. 14,17,21,22,42 Three out of four patients (75%) that were euthyroid prior to SBRT developed hypothyroidism and required thyroid hormonal supplements.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of stereotactic body radiation therapy (SBRT) for the treatment of canine thyroid carcinoma

Lee

LaRue

Séguin

et al. 2020

Vet Comparative Oncology

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Thyroid carcinoma develops spontaneously in dogs, with only 25% to 50% of cases amenable to surgery at diagnosis. Local control for unresectable tumours can be provided with external beam radiotherapy. The aim of this retrospective study is to describe the safety and efficacy of stereotactic body radiation therapy (SBRT) for treatment of canine thyroid carcinoma. Twenty-three dogs met inclusion criteria; median tumour volume before SBRT was 129.9 cm 3 (range, 2.7-452.8 cm 3). Sixteen patients (70%) had unresectable tumours. Pulmonary metastasis was present or suspected in 10 patients (44%) before SBRT. Patients were prescribed 15 to 40 Gy to targeted tumour volume in one to five fractions. Twenty patients evaluated had overall response rate of 70% (complete response, n = 4; partial response, n = 10). Thirteen out of sixteen (81%) symptomatic patients had clinical improvement within a median time of 16 days (range, 2-79 days). Median progression free survival (MPFS) was 315 days. Median survival time (MST) was 362 days. Nine patients (39%) had grade 1 acute radiation toxicity. Three patients had grade 1 late radiation toxicity (two leukotrichia and one [4%] with intermittent cough). Responders had significantly longer MPFS (362 vs 90 days; HR 4.3; 95% CI 1.4-13.5; P = .013) and MST (455 vs 90 days; HR 2.9; 95% CI 1-8.4; P = .053). Presenting with metastasis was not a significant negative prognostic factor (MST 347 vs 348 days without metastasis; P = .352). SBRT is a safe and effective treatment modality for non-resectable canine thyroid carcinoma.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of stereotactic body radiation therapy (SBRT) for the treatment of canine thyroid carcinoma

Lee

LaRue

Séguin

et al. 2020

Vet Comparative Oncology

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“…Further studies in canine oral melanomas should shed some light on these aspects, revealing recurrent mutations with strong effect in specific locations and specific breeds, reflecting different genetic backgrounds that are easiest to investigate in dog breeds. These data were very recently enriched by comparative expression profiling of 28 cases of oral malignant melanoma, comparing metastatic/primary situations [86].…”

Section: Canine Mucosal Melanomamentioning

confidence: 99%

Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison

Prouteau

André

2019

Genes

106

110

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Despite recent genetic advances and numerous ongoing therapeutic trials, malignant melanoma remains fatal, and prognostic factors as well as more efficient treatments are needed. The development of such research strongly depends on the availability of appropriate models recapitulating all the features of human melanoma. The concept of comparative oncology, with the use of spontaneous canine models has recently acquired a unique value as a translational model. Canine malignant melanomas are naturally occurring cancers presenting striking homologies with human melanomas. As for many other cancers, dogs present surprising breed predispositions and higher frequency of certain subtypes per breed. Oral melanomas, which are much more frequent and highly severe in dogs and cutaneous melanomas with severe digital forms or uveal subtypes are subtypes presenting relevant homologies with their human counterparts, thus constituting close models for these human melanoma subtypes. This review addresses how canine and human melanoma subtypes compare based on their epidemiological, clinical, histological, and genetic characteristics, and how comparative oncology approaches can provide insights into rare and poorly characterized melanoma subtypes in humans that are frequent and breed-specific in dogs. We propose canine malignant melanomas as models for rare non-UV-induced human melanomas, especially mucosal melanomas. Naturally affected dogs offer the opportunity to decipher the genetics at both germline and somatic levels and to explore therapeutic options, with the dog entering preclinical trials as human patients, benefiting both dogs and humans.

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“…On the contrary, other genes such as MDM2 (27,28) or CDK4 (8, 28), were not confirmed by our study. Finally, it is noteworthy that other genes involved in CNAs such as ADAM10, and genes belonging to gene families SNORA, SNORD, SLC25A, RPL, and RBM, have been recently shown to be highly expressed in metastatic COMs (32).…”

Section: Comparison With Published Canine Cnasmentioning

confidence: 99%

Array Comparative Genomic Hybridization Analysis Reveals Significantly Enriched Pathways in Canine Oral Melanoma

et al. 2019

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Human Mucosal Melanoma (hMM) is an aggressive neoplasm of neuroectodermal origin with distinctive features from the more common cutaneous form of malignant melanoma (cMM). At the molecular level, hMMs are characterized by large chromosomal aberrations rather than single-nucleotide mutations, typically observed in cMM. Given the scarcity of available cases, there have been many attempts to establish a reliable animal model. In pet dogs, Canine Oral Melanoma (COM) is the most common malignant tumor of the oral cavity, sharing clinical and histological aspects with hMM.To improve the knowledge about COM's genomic DNA alterations, in the present work, formalin-fixed, paraffin-embedded (FFPE) samples of COM from different European archives were collected to set up an array Comparative Genomic Hybridization (aCGH) analysis to estimate recurrent Copy Number Aberrations (CNAs). DNA was extracted in parallel from tumor and healthy fractions and 19 specimens were successfully submitted to labeling and competitive hybridization. Data were statistically analyzed through GISTIC2.0 and a pathway-enrichment analysis was performed with ClueGO. Recurrent gained regions were detected, affecting chromosomes CFA 10, 13 and 30, while lost regions involved chromosomes CFA 10, 11, 22, and 30. In particular, CFA 13 showed a whole-chromosome gain in 37% of the samples, while CFA 22 showed a whole-chromosome loss in 25%. A distinctive sigmoidal trend was observed in CFA 10 and 30 in 25 and 30% of the samples, respectively. Comparative analysis revealed that COM and hMM share common chromosomal changes in 32 regions. MAPK-and PI3K-related genes were the most frequently involved, while pathway analysis revealed statistically significant perturbation of cancer-related biological processes such as immune response, drug metabolism, melanocytes homeostasis, and neo-angiogenesis. The latter is a new evidence of a significant involvement of neovascularization-related pathways in COMs and can provide the rationale for future application in anti-cancer targeted therapies.

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Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression

Cited by 20 publications

References 122 publications

Safety and efficacy of stereotactic body radiation therapy (SBRT) for the treatment of canine thyroid carcinoma

Safety and efficacy of stereotactic body radiation therapy (SBRT) for the treatment of canine thyroid carcinoma

Canine Melanomas as Models for Human Melanomas: Clinical, Histological, and Genetic Comparison

Array Comparative Genomic Hybridization Analysis Reveals Significantly Enriched Pathways in Canine Oral Melanoma

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