Cross‐species models of human melanoma

Weyden, Louise van der; Patton, E. Elizabeth; Wood, Geoffrey A.; Foote, A. K.; Brenn, Thomas; Arends, Mark J.; Adams, David J.

doi:10.1002/path.4632

Cited by 66 publications

(59 citation statements)

References 138 publications

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“…This suggests the existence of a different biological pathway in the melanoma development at early ages not linked to coloration, distinct from the mostly benign condition in grey horses linked with the age and greying regulation (e.g. dermal melanomatosis) [17,22,23]. In fact, the interaction age/coat colour was not only significant in the S3 population for Melanoma.…”

Section: Discussionmentioning

confidence: 91%

Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses

Sánchez‐Guerrero

Solé

Azor

et al. 2019

Equine Veterinary Journal

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Summary Background Vitiligo and melanoma are relatively common disorders in grey Pura Raza Español horses and other horse breeds with grey‐coloured coats. Objectives To determine the breed prevalence, environmental risks factors and estimate the genetic parameters for vitiligo and melanoma in Pura Raza Español horses. Study design Retrospective cohort study. Methods We analysed data from a large worldwide population of Pura Raza Español horses. The database included the vitiligo and melanoma scores, on either a four‐ or six‐point linear scale, of 11,436 horses. Genetic parameters were estimated using a Bayesian genetic animal model including the four associated environmental risk factors as systematic effects. Inbreeding was used as a covariate, and animal and residual effects were included as random effects. Results Of the horses included in the study, 2.8 and 20.5% showed some traces of vitiligo around the eyes and mouth, respectively, while 1.6% showed varying degrees of melanoma. Age, coat colour and inbreeding were significantly associated with the three outcomes studied. The estimated heritability for the whole population was 0.09 (s.d. +0.019), 0.44 (s.d. +0.031) and 0.13 (s.d. +0.037), for eye vitiligo score, nostril vitiligo score and melanoma scores respectively. The genetic correlations ranged from 0.42 (s.d. +0.084) between eye and nostril vitiligo score to 0.15 (s.d. +0.096) between nostril vitiligo and melanoma. Main limitations Vitiligo scores for the perianal regions were not collected. The veterinarian responsible for each assessment was not recorded. Conclusions Vitiligo and melanoma are prevalent in this population and those environmental risk factors and genetics both have an effect on the clinical expression of the diseases. These findings may help to reduce prevalence through breeding programmes.

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Section: Discussionmentioning

confidence: 91%

Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses

Sánchez‐Guerrero

Solé

Azor

et al. 2019

Equine Veterinary Journal

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“…To further investigate the influence of melanin on SWI, we performed a complementing in vitro experiment with a melanin-producing melanoma cell line. The SWI signal behavior of B16 melanoma cells, a common preclinical model of MM, 25 was compared with nonmelanotic U87 glioma cells, 26 which served as a negative control at 9.4 T and 3 T. Erythrocytes that are known to cause SWI blooming artifacts were used as a positive control. B16 melanoma cells, despite the high production of black melanin pigment, only showed a moderate signal drop in SWI compared with erythrocytes at 3 T (Fig.…”

Section: In Vitro Analysis Of the Melanin Susceptibility Effectmentioning

confidence: 99%

Susceptibility‐weighted imaging in malignant melanoma brain metastasis

Schwarz

Niederle

Münch

et al. 2019

Magnetic Resonance Imaging

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Background The value of cerebral susceptibility‐weighted imaging (SWI) in malignant melanoma (MM) patients remains controversial and the effect of melanin on SWI is not well understood. Purpose To systematically analyze the spectrum of intracerebral findings in MM brain metastases (BM) on SWI and to determine the diagnostic value of SWI. Study Type Retrospective. Population/Subjects In all, 100 patients with melanoma BM (69 having received radiotherapy [RT] and 31 RT‐naïve) and a control group of 100 melanoma patients without BM were included. For detailed analysis of signal characteristics, 175 metastases were studied. Field Strength/Sequence Gradient echo SWI sequence at 1.5, 3.0, and 9.4 T. Assessment Signal characteristics from melanotic and amelanotic BMs on SWI with a focus on blooming artifacts were analyzed, as well as the presence and longitudinal dynamics of isolated SWI blooming artifacts in patients with and without BM. Statistical Tests Chi‐squared and Student's t‐test were used for contingency table measures and group data of signal and clinical characteristics, respectively. Results Melanotic and amelanotic metastases did not show significant differences of SWI blooming artifacts (38% vs. 43%, P = 0.61). Most metastases without an initial SWI artifact developed a signal dropout during follow‐up (80%; 65/81). Isolated SWI artifacts were detected more frequently in patients with BM (20 vs. 9, P = 0.03), of which the majority were found in patients who had received RT (17 vs. 3, P = 0.08). None of these isolated SWI blooming artifacts turned into overt metastases over time (median follow‐up: 8.5 months). Similar findings persisted as remnants of successfully treated metastases (88%; 7/8). Data Conclusion We conclude that SWI provides little additional diagnostic benefit over standard T1‐weighted imaging, as melanin content alone does not cause diagnostically relevant SWI blooming. Signal transition of SWI may rather indicate secondary phenomena like microbleeding and/or metal scavenging. Our results suggest that isolated SWI artifacts do not constitute vital tumor tissue but represent unspecific microbleedings, RT‐related parenchymal changes or posttherapeutic remnants of former metastatic lesions. Level of Evidence: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1251–1259.

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“…The highly aggressive biological behavior of hMMs (11) and the scarcity of available cases led to many attempts to establish a reliable animal model for the study of this life-threatening disease. Various in vivo models have been proposed for melanocytic derived-tumors through genetically engineered mice and zebrafish (12). Relevant limitations of these models are the lack of tumor population heterogeneity, combined with the longtime of tumor formation (12,13).…”

Section: Introductionmentioning

confidence: 99%

“…Various in vivo models have been proposed for melanocytic derived-tumors through genetically engineered mice and zebrafish (12). Relevant limitations of these models are the lack of tumor population heterogeneity, combined with the longtime of tumor formation (12,13). Altogether, these studies revealed the necessity of a spontaneous tumor model in non-engineered animals.…”

Section: Introductionmentioning

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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Cross‐species models of human melanoma

Cited by 66 publications

References 138 publications

Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses

Genetic and environmental risk factors for vitiligo and melanoma in Pura Raza Español horses

Susceptibility‐weighted imaging in malignant melanoma brain metastasis

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

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