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

Ricardo Errazquin; Angustias Page; Anna Suñol; Carmen Segrelles; Estela Carrasco; Jorge Peral; Alicia Garrido-Aranda; Sonia Del Marro; Jessica Ortiz; Corina Lorz; Jordi Minguillon; Jordi Surrallés i Calonge; Cristina Belendez; Martina Álvarez; Judith Balmaña Gelpí; Ana Bravo; Angel Ramirez; Ramon Garcia-Escudero

doi:10.1016/j.oraloncology.2022.106184

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

Ricardo Errazquin, Angustias Page, Anna Suñol, Carmen Segrelles, Estela Carrasco, Jorge Peral, Alicia Garrido-Aranda, Sonia Del Marro, Jessica Ortiz, Corina Lorz, Jordi Minguillon, Jordi Surrallés i Calonge, Cristina Belendez, Martina Álvarez, Judith Balmaña Gelpí, Ana Bravo, Angel Ramirez, Ramon Garcia-Escudero

Departamento de Genética y Microbiología

Hospital Universitario Vall d'Hebron (HUVH)

Producción científica: Contribución a una revista › Artículo › Investigación › revisión exhaustiva

5 Citas (Scopus)

Resumen

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.

Idioma original	Inglés
Publicación	Oral Oncology
Volumen	134
DOI	https://doi.org/10.1016/j.oraloncology.2022.106184
Estado	Publicada - 2022

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Errazquin, R., Page, A., Suñol, A., Segrelles, C., Carrasco, E., Peral, J., Garrido-Aranda, A., Del Marro, S., Ortiz, J., Lorz, C., Minguillon, J., Surrallés i Calonge, J., Belendez, C., Álvarez, M., Balmaña Gelpí, J., Bravo, A., Ramirez, A., & Garcia-Escudero, R. (2022). Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia. Oral Oncology, 134. https://doi.org/10.1016/j.oraloncology.2022.106184

@article{ceb86ff81a864178899e6ac6f729803a,

title = "Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia",

abstract = "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.",

keywords = "Fanconi anemia, Head and neck squamous cell carcinoma, Oral squamous cell carcinoma, Mouse model, Oral mucosa, FANCA, TP53, Trp53, P53, Mutation",

author = "Ricardo Errazquin and Angustias Page and Anna Su{\~n}ol and Carmen Segrelles and Estela Carrasco and Jorge Peral and Alicia Garrido-Aranda and {Del Marro}, Sonia and Jessica Ortiz and Corina Lorz and Jordi Minguillon and {Surrall{\'e}s i Calonge}, Jordi and Cristina Belendez and Martina {\'A}lvarez and {Balma{\~n}a Gelp{\'i}}, Judith and Ana Bravo and Angel Ramirez and Ramon Garcia-Escudero",

year = "2022",

doi = "10.1016/j.oraloncology.2022.106184",

language = "English",

volume = "134",

journal = "Oral Oncology",

issn = "1368-8375",

publisher = "Elsevier Limited",

}

Errazquin, R, Page, A, Suñol, A, Segrelles, C, Carrasco, E, Peral, J, Garrido-Aranda, A, Del Marro, S, Ortiz, J, Lorz, C, Minguillon, J, Surrallés i Calonge, J, Belendez, C, Álvarez, M, Balmaña Gelpí, J, Bravo, A, Ramirez, A & Garcia-Escudero, R 2022, 'Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia', Oral Oncology, vol. 134. https://doi.org/10.1016/j.oraloncology.2022.106184

TY - JOUR

T1 - Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia

AU - Errazquin, Ricardo

AU - Page, Angustias

AU - Suñol, Anna

AU - Segrelles, Carmen

AU - Carrasco, Estela

AU - Peral, Jorge

AU - Garrido-Aranda, Alicia

AU - Del Marro, Sonia

AU - Ortiz, Jessica

AU - Lorz, Corina

AU - Minguillon, Jordi

AU - Surrallés i Calonge, Jordi

AU - Belendez, Cristina

AU - Álvarez, Martina

AU - Balmaña Gelpí, Judith

AU - Bravo, Ana

AU - Ramirez, Angel

AU - Garcia-Escudero, Ramon

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Fanconi anemia

KW - Head and neck squamous cell carcinoma

KW - Oral squamous cell carcinoma

KW - Mouse model

KW - Oral mucosa

KW - FANCA

KW - TP53

KW - Trp53

KW - P53

KW - Mutation

U2 - 10.1016/j.oraloncology.2022.106184

DO - 10.1016/j.oraloncology.2022.106184

M3 - Article

C2 - 36191479

SN - 1368-8375

VL - 134

JO - Oral Oncology

JF - Oral Oncology

ER -

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

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