Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid
Association between p53-binding protein 1 expression and genomic instability in oncocytic follicular adenoma of the thyroid
复制标题
DOI：
10.1507/endocrj.ej15-0629
复制
发表时间：
2016-05-20
影响因子：
2
通讯作者：
Nakashima, Masahiro
中科院分区：
文献类型：
--
作者：
Mussazhanova, Zhanna;Akazawa, Yuko;Nakashima, Masahiro
甲状腺嗜酸细胞性滤泡性腺瘤是一种起源于滤泡细胞的肿瘤，主要由大的多角形细胞组成，细胞质呈嗜酸性和颗粒状。然而，这些肿瘤的病理特征在很大程度上是未探索的。癌症的发生和发展都可能是由可诱导基因组不稳定性的基因突变的积累引起的。因此，本研究的目的是评估嗜酸细胞FA的基因组不稳定性的程度。由于p53结合蛋白1（53 BP 1）在核灶中的存在已被发现反映了由各种应激引发的DNA双链断裂，因此在嗜酸细胞和常规FA中评估了53 BP-1的免疫荧光表达模式。与DNA拷贝数畸变（CNA）的程度的关联也进行了评估，使用基于阵列的比较基因组杂交。来自该研究的数据表明增加的53 BP 1表达（即，与常规FA相比，嗜酸细胞FA的核灶中CNA的表达是“不稳定的”），并且CNA的发生率更高。也有一个特别关注的扩增染色体1 p36在嗜酸细胞FA，其中包括基因座的肿瘤蛋白73，p53家族的成员牵连作为一个因素，在恶性肿瘤的发展。进一步的评估显示，不稳定的53 BP 1表达与肿瘤蛋白73的表达水平具有显著的正相关性。这些数据表明，与传统FA相比，嗜酸细胞FA的基因组不稳定性水平更高，并且嗜酸细胞FA与肿瘤蛋白73的异常扩增之间可能存在关系。
Oncocytic follicular adenomas (FAs) of the thyroid are neoplasms of follicular cell origin that are predominantly composed of large polygonal cells with eosinophilic and granular cytoplasm. However, the pathological characteristics of these tumors are largely unexplored. Both the initiation and progression of cancer can be caused by an accumulation of genetic mutations that can induce genomic instability. Thus, the aim of this study was to evaluate the extent of genomic instability in oncocytic FA. As the presence of p53-binding protein 1 (53BP1) in nuclear foci has been found to reflect DNA double-strand breaks that are triggered by various stresses, the immunofluorescence expression pattern of 53BP-1 was assessed in oncocytic and conventional FA. The association with the degree of DNA copy number aberration (CNA) was also evaluated using array-based comparative genomic hybridization. Data from this study demonstrated increased 53BP1 expression (i.e., "unstable" expression) in nuclear foci of oncocytic FA and a higher incidence of CNAs compared with conventional FA. There was also a particular focus on the amplification of chromosome 1p36 in oncocytic FA, which includes the locus for Tumor protein 73, a member of the p53 family implicated as a factor in the development of malignancies. Further evaluations revealed that unstable 53BP1 expression had a significant positive correlation with the levels of expression of Tumor protein 73. These data suggest a higher level of genomic instability in oncocytic FA compared with conventional FA, and a possible relationship between oncocytic FA and abnormal amplification of Tumor protein 73.