Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets

Prouteau, Anaïs; Mottier, Stéphanie; Primot, Aline; Cadieu, Édouard; Bachelot, Laura; Botherel, Nadine; Cabillic, Florian; Houel, Armel; Cornevin, Laurence; Kergal, Camille; Corre, Sébastien; Abadie, Jérôme; Hitte, Christophe; Gilot, David; Lindblad‐Toh, Kerstin; André, Catherine; Derrien, Thomas; Hédan, Benoît

doi:10.3390/cancers14020276

Cited by 17 publications

(3 citation statements)

References 98 publications

(184 reference statements)

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“…Rapid genetic tumor modeling in zebrafish has contributed to major discoveries in CM biology 10, 11, 12 , the functional role of CRKL in acral melanoma 13 , as well as the role of SPRED1 deletion in KIT inhibitor resistance in MM 5 . Studies of spontaneously occurring MM in canines have been fruitful 14 , but there remains a need to develop genetically engineered animal models to determine functional drivers of MM in patients.…”

Section: Main Textmentioning

confidence: 99%

Specific oncogene activation of the cell of origin in mucosal melanoma

Babu,

Chen,

Robitschek

et al. 2024

Preprint

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Mucosal melanoma (MM) is a deadly cancer derived from mucosal melanocytes. To test the consequences of MM genetics, we developed a zebrafish model in which all melanocytes experienced CCND1 expression and loss of PTEN and TP53. Surprisingly, melanoma only developed from melanocytes lining internal organs, analogous to the location of patient MM. We found that zebrafish MMs had a unique chromatin landscape from cutaneous melanoma. Internal melanocytes could be labeled using a MM-specific transcriptional enhancer. Normal zebrafish internal melanocytes shared a gene expression signature with MMs. Patient and zebrafish MMs have increased migratory neural crest gene and decreased antigen presentation gene expression, consistent with the increased metastatic behavior and decreased immunotherapy sensitivity of MM. Our work suggests the cell state of the originating melanocyte influences the behavior of derived melanomas. Our animal model phenotypically and transcriptionally mimics patient tumors, allowing this model to be used for MM therapeutic discovery.

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Section: Main Textmentioning

confidence: 99%

Specific oncogene activation of the cell of origin in mucosal melanoma

Babu,

Chen,

Robitschek

et al. 2024

Preprint

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“…A recent study revealed that TRPM7 was involved in the proliferation of canine and human non-UV-induced melanomas. TRPM7 genes were suggested as candidate oncogenes for human mucosal melanoma [189] (Table 10).…”

Section: Prostate Cancermentioning

confidence: 99%

The Role of TRPM7 in Oncogenesis

Köles,

Ribiczey,

Szebeni

et al. 2024

IJMS

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This review summarizes the current understanding of the role of transient receptor potential melastatin-subfamily member 7 (TRPM7) channels in the pathophysiology of neoplastic diseases. The TRPM family represents the largest and most diverse group in the TRP superfamily. Its subtypes are expressed in virtually all human organs playing a central role in (patho)physiological events. The TRPM7 protein (along with TRPM2 and TRPM6) is unique in that it has kinase activity in addition to the channel function. Numerous studies demonstrate the role of TRPM7 chanzyme in tumorigenesis and in other tumor hallmarks such as proliferation, migration, invasion and metastasis. Here we provide an up-to-date overview about the possible role of TRMP7 in a broad range of malignancies such as tumors of the nervous system, head and neck cancers, malignant neoplasms of the upper gastrointestinal tract, colorectal carcinoma, lung cancer, neoplasms of the urinary system, breast cancer, malignant tumors of the female reproductive organs, prostate cancer and other neoplastic pathologies. Experimental data show that the increased expression and/or function of TRPM7 are observed in most malignant tumor types. Thus, TRPM7 chanzyme may be a promising target in tumor therapy.

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“…In recent years, some progress has been made in research on canine genomics [ 3 , 4 , 5 ] and transcriptomics analysis [ 6 ]. And the treatment of canine melanoma at the molecular level [ 7 , 8 ], immunotherapy [ 9 , 10 , 11 ], and other novel therapeutic approaches [ 12 , 13 , 14 , 15 ] have seen some progress.…”

Section: Introductionmentioning

confidence: 99%

Establishment of Canine Oral Mucosal Melanoma Cell Lines and Their Xenogeneic Animal Models

Li,

Liu,

et al. 2024

Cells

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Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100β), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma.

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Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets

Cited by 17 publications

References 98 publications

Specific oncogene activation of the cell of origin in mucosal melanoma

Specific oncogene activation of the cell of origin in mucosal melanoma

The Role of TRPM7 in Oncogenesis

Establishment of Canine Oral Mucosal Melanoma Cell Lines and Their Xenogeneic Animal Models

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