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

被引：5

作者：

Errazquin, Ricardo ^{[1
]}

Page, Angustias ^{[1
,2
,3
]}

Sunol, Anna

Segrelles, Carmen ^{[1
,2
,3
]}

Carrasco, Estela ^{[4
]}

Peral, Jorge ^{[3
]}

Garrido-Aranda, Alicia ^{[5
]}

Del Marro, Sonia ^{[3
]}

Ortiz, Jessica ^{[3
]}

Lorz, Corina ^{[1
,2
,3
]}

Minguillon, Jordi ^{[6
,7
]}

Surralles, Jordi ^{[6
,7
]}

Belendez, Cristina ^{[7
,8
,9
,10
]}

Alvarez, Martina ^{[5
]}

Balmana, Judith ^{[1
,4
]}

Bravo, Ana ^{[11
]}

Ramirez, Angel ^{[1
,2
,3
]}

Garcia-Escudero, Ramon ^{[1
,2
,3
]}

机构：

[1] Univ Hosp 12 Octubre, Res Inst Hosp Octubre 12 imas12, Cordoba S-N, Madrid 28041, Spain

[2] Ctr Invest Biomed Red Canc CIBERONC, Madrid 28029, Spain

[3] CIEMAT Ctr Invest Energet Medioambientales & Tecno, Biomed Oncol Unit, Ave Complutense 40, Madrid 28040, Spain

[4] VHIO, Med Oncol Dept, Hereditary Canc Genet Grp, Barcelona, Spain

[5] Ctr Invest Med Sanitarias CIMES, Malaga, Spain

[6] Hosp St Creu i St Pau, St Pau Biomed Res Inst IIB St Pau, Join Res Unit Genom Med UAB, Barcelona 08041, Spain

[7] Ctr Invest Biomed Enfermedades Raras CIBERER, Madrid 28029, Spain

[8] Hosp Gen Univ Gregorio Maranon, Pediat Hematol & Oncol, Madrid, Spain

[9] Univ Complutense Madrid, Fac Med, Madrid, Spain

[10] Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain

[11] Univ Santiago Compostela, Fac Vet Med, Dept Anat, Lab Pathol Phenotyping Genet Engn Mice, Lugo 27002, Spain

来源：

ORAL ONCOLOGY | 2022年 / 134卷

关键词：

Fanconi anemia; Head and neck squamous cell carcinoma; Oral squamous cell carcinoma; Mouse model; Oral mucosa; FANCA; TP53; Trp53; p53; Mutation; TARGETED DISRUPTION; HEAD; P53; CANCER; MICE; DNA;

D O I：

10.1016/j.oraloncology.2022.106184

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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(F2-10)/ (F2-10)), 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(F2-10/F2-10) mice constitute the first animal model of spontaneous OSCC in FA.

引用

页数：7

共 42 条

[41]

Webster ALH, 2021, BIORXIV, V2021

[42] Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia [J].

Wong, JCY ;

Alon, N ;

Mckerlie, C ;

Huang, JR ;

Meyn, MS ;

Buchwald, M .

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