Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations
Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations
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DOI：
10.1038/ng0297-170
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发表时间：
1997-02-01
期刊：
影响因子：
30.8
通讯作者：
VandeVen, WJM
中科院分区：
文献类型：
--
作者：
Kas, K;Voz, ML;VandeVen, WJM
唾液腺多形性腺瘤是一种主要发生在大唾液腺和小唾液腺的良性上皮肿瘤(1)。这是目前为止最常见的唾液腺肿瘤。显微镜下，多形性腺瘤表现出明显的组织学多样性，上皮、肌上皮和间充质成分具有多种模式。除了具有正常核型的细胞遗传学亚群外，多相性腺瘤的特征是反复发生的染色体重排，特别是相互易位，断点按频率顺序在8q12、3p21和12q13-15（2,3）。最常见的异常是倒数t(3;8)（p21;q12）。我们在这里证明了t(3;8)（p21;q12）导致启动子在PLAG1和β -连环蛋白（CTNNB1）基因之间交换，PLAG1是一种新型的发育调节锌指基因，位于8q12， CTNNB1是一种蛋白质界面，在WG/WNT信号通路中起作用，并在胚胎发生过程中指定细胞命运(4)。融合发生在两个基因的5'-非编码区，交换调控元件，同时保留编码序列。由于t(3;8)(p21;q12)， PLAG1被激活，CTNNB1的表达水平降低。PLAG1的激活也在一个易位变异的腺瘤中观察到（8;15）（q12;q14）。我们的研究结果表明，启动子交换引起的PLAG1激活是唾液腺肿瘤发生的关键事件。
Pleiomorphic adenoma of the salivary glands is a benign epithelial tumour occurring primarily in the major and minor salivary glands(1). It is by far the most common type of salivary gland tumour. Microscopically, pleiomorphic adenomas show a marked histological diversity with epithelial, myoepithelial and mesenchymal components in a variety of patterns. In addition to a cytogenetic subgroup with normal karyotypes, pleiomorphic adenomas are characterized by recurrent chromosome rearrangements, particularly reciprocal translocations, with breakpoints at 8q12, 3p21, and 12q13-15, in that order of frequency(2,3). The most common abnormality is a reciprocal t(3;8)(p21;q12). We here demonstrate that the t(3;8)(p21;q12) results in promoter swapping between PLAG1, a novel, developmentally regulated zinc finger gene at 8q12, and the constitutively expressed gene for beta-catenin (CTNNB1), a protein interface functioning in the WG/WNT signalling pathway and specification of cell fate during embryogenesis(4). Fusions occur in the 5'-non-coding regions of both genes, exchanging regulatory control elements while preserving the coding sequences. Due to the t(3;8)(p21;q12), PLAG1 is activated and expression levels of CTNNB1 are reduced. Activation of PLAG1 was also observed in an adenoma with a variant translocation t(8;15)(q12;q14). Our results indicate that PLAG1 activation due to promoter swapping is a crucial event in salivary gland tumourigenesis.