Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia

Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxi...

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Detalles Bibliográficos
Autores: Errazquin, Ricardo, Page, Angustias, Suñol Camas, Anna, Segrelles, Carmen, Carrasco, Estela|||0000-0003-1964-7675, Peral, Jorge, Garrido-Aranda, Alicia, Del Marro, Sonia, Ortiz, Jessica, Lorz, Corina|||0000-0001-8214-9076, Minguillon, Jordi, Surralles, Jordi|||0000-0002-4041-7519, Belendez, Cristina, Álvarez, Martina, Balmaña Gelpí, Judith|||0000-0002-0762-6415, Bravo, Ana|||0000-0002-2420-1419, Ramirez, Angel, Garcia-Escudero, Ramon|||0000-0001-5640-6542
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:280865
Acceso en línea:https://ddd.uab.cat/record/280865
https://dx.doi.org/urn:doi:10.1016/j.oraloncology.2022.106184
Access Level:acceso abierto
Palabra clave:Fanconi anemia
Head and neck squamous cell carcinoma
Oral squamous cell carcinoma
Mouse model
Oral mucosa
FANCA
TP53
Trp53
P53
Mutation
Descripción
Sumario:Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca ) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of Trp53 gene in oral mucosa (K14cre;Trp53), they spontaneously developed OSCC with high penetrance and a median latency of less than ten months. Tumors were well differentiated and expressed markers of squamous differentiation, such as keratins K5 and K10. In conclusion, Fanca and Trp53 genes cooperate to suppress oral cancer in mice, and Fanca;K14cre;Trp53 mice constitute the first animal model of spontaneous OSCC in FA.

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