Abstract：
BACKGROUND: Testicular germ cell tumor (TGCT) is the most common type of tumor in young men. Type II germ cell tumors including postpubertal-type teratomas are derived from the germ cell neoplasia in situ (GCNIS), whereas prepubertal-type teratomas arise independently of the GCNIS. The consomic mouse strain 129.MOLF-Chr19 (M19) is a suitable murine model of such tumors, but its characterization remains incomplete.
OBJECTIVE: Here, we interrogated the suitability of testicular tumors in M19 mice as a model of human TGCT by analyzing their histological features and gene expression signature.
METHODS: Testes collected from M19 mice of different ages were categorized by macroscopic appearance based on size and the degree of suspected tumorigenesis. Histological sections from selected tumors were stained with Hematoxylin and Eosin, and expression of genes associated with tumorigenesis was determined in frozen tissue samples from a large range of tumors of different subclasses using RT-qPCR and Fluidigm Dynamic Arrays.
RESULTS: Macroscopically, testicular specimens appeared very heterogeneous concerning size and signs indicating the presence of a tumor. Histological analysis confirmed the development of teratomas with areas of cells corresponding to all three germ cell layers. Gene expression analyses indicated upregulation of markers related to proliferation, vascular invasive potential and pluripotency, and revealed a strong correlation of gene expression with tumor size and a significant intercorrelation of individual genes.
CONCLUSIONS: TGCT in M19 mice is reminiscent of human testicular teratomas presenting with areas of cells derived from all germ layers and showing a typical gene signature. We thus confirm that these mice can serve as a suitable murine model of pure teratomas for preclinical research.
OBJECTIVE: Here, we interrogated the suitability of testicular tumors in M19 mice as a model of human TGCT by analyzing their histological features and gene expression signature.
METHODS: Testes collected from M19 mice of different ages were categorized by macroscopic appearance based on size and the degree of suspected tumorigenesis. Histological sections from selected tumors were stained with Hematoxylin and Eosin, and expression of genes associated with tumorigenesis was determined in frozen tissue samples from a large range of tumors of different subclasses using RT-qPCR and Fluidigm Dynamic Arrays.
RESULTS: Macroscopically, testicular specimens appeared very heterogeneous concerning size and signs indicating the presence of a tumor. Histological analysis confirmed the development of teratomas with areas of cells corresponding to all three germ cell layers. Gene expression analyses indicated upregulation of markers related to proliferation, vascular invasive potential and pluripotency, and revealed a strong correlation of gene expression with tumor size and a significant intercorrelation of individual genes.
CONCLUSIONS: TGCT in M19 mice is reminiscent of human testicular teratomas presenting with areas of cells derived from all germ layers and showing a typical gene signature. We thus confirm that these mice can serve as a suitable murine model of pure teratomas for preclinical research.
摘要：
背景：睾丸生殖细胞肿瘤（TGCT）是年轻男性中最常见的肿瘤类型。II型生殖细胞肿瘤包括青春期后畸胎瘤来源于生殖细胞原位瘤（GCNIS），而青春期前型畸胎瘤的产生独立于GCNIS。consomic小鼠品系129。MOLF-Chr19（M19）是这种肿瘤的合适的小鼠模型，但是它的表征仍然不完整。
目标：这里，我们通过分析M19小鼠睾丸肿瘤的组织学特征和基因表达特征,研究了其作为人类TGCT模型的适用性.
方法：从不同年龄的M19小鼠收集的睾丸根据大小和可疑肿瘤发生的程度通过宏观外观进行分类。选定肿瘤的组织学切片用苏木精和伊红染色，使用RT-qPCR和Fluidigm动态阵列在来自不同亚类的大范围肿瘤的冷冻组织样品中确定与肿瘤发生相关的基因的表达。
结果：宏观上，睾丸标本在大小和指示存在肿瘤的体征方面表现出非常不均匀。组织学分析证实了畸胎瘤的发展，其细胞面积对应于所有三个生殖细胞层。基因表达分析表明与增殖相关的标志物上调，血管侵入潜能和多能性，并揭示了基因表达与肿瘤大小的强相关性以及单个基因的显着相关性。
结论：M19小鼠的TGCT让人想起人睾丸畸胎瘤，其细胞区域来自所有胚层，并显示出典型的基因特征。因此，我们确认这些小鼠可以作为纯畸胎瘤的合适小鼠模型用于临床前研究。
目标：这里，我们通过分析M19小鼠睾丸肿瘤的组织学特征和基因表达特征,研究了其作为人类TGCT模型的适用性.
方法：从不同年龄的M19小鼠收集的睾丸根据大小和可疑肿瘤发生的程度通过宏观外观进行分类。选定肿瘤的组织学切片用苏木精和伊红染色，使用RT-qPCR和Fluidigm动态阵列在来自不同亚类的大范围肿瘤的冷冻组织样品中确定与肿瘤发生相关的基因的表达。
结果：宏观上，睾丸标本在大小和指示存在肿瘤的体征方面表现出非常不均匀。组织学分析证实了畸胎瘤的发展，其细胞面积对应于所有三个生殖细胞层。基因表达分析表明与增殖相关的标志物上调，血管侵入潜能和多能性，并揭示了基因表达与肿瘤大小的强相关性以及单个基因的显着相关性。
结论：M19小鼠的TGCT让人想起人睾丸畸胎瘤，其细胞区域来自所有胚层，并显示出典型的基因特征。因此，我们确认这些小鼠可以作为纯畸胎瘤的合适小鼠模型用于临床前研究。
