Identification of candidates for tumor-specific alternative splicing in the thyroid
Identification of candidates for tumor-specific alternative splicing in the thyroid
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DOI：
10.1002/gcc.20316
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发表时间：
2006-06-01
影响因子：
3.7
通讯作者：
Cerutti, JM
中科院分区：
文献类型：
--
作者：
Guimaraes, GS;Latini, FRM;Cerutti, JM
选择性剪接是外显子连接处的差异加工，以从一个基因产生新的转录变体。然而，一些异常剪接已被证明是癌症特异性的。这些特定的剪接变异的鉴定将为了解正常细胞生理学的分子机制以及疾病过程提供重要的见解。为了获得关于选择性剪接是否与甲状腺肿瘤发生有关的知识，我们使用我们的预测数据库来选择分析目标。根据它们在甲状腺文库中的表达和/或它们在先前与致癌作用相关的基因中的起源，选择了15种新的选择性剪接异构体。使用一组66例正常、良性和恶性甲状腺组织样本，通过RT-PCR证实了13个IS基因的新剪接事件（验证率为87%）。此外，新的选择性剪接异构体没有预测的系统和以前没有在公共数据库中描述的被确定。五个基因（PTPN 18，AB 13 BP，PFDN 5，SULF 2和ST 5）提出了新的和/或额外的不可预测的亚型之间的恶性和良性或正常甲状腺组织的差异表达，通过测序证实。PTPN 18、AB 13 BP和PFDN 5显示了统计学上显著的差异剪接谱。此外，实时PCR分析显示，恶性病变中另一种PFDN 5变体的表达高于良性病变或正常组织。(c)2006 Wiley-Liss，Inc.
Alternative splicing is the differential processing of exon junctions to produce a new transcript variant from one gene. Some aberrant splicing, however, has been shown to be cancer specific. Identification of these specific splice variations will provide important insight into the molecular mechanism of normal cellular physiology as well as the disease processes. To gain knowledge about whether alternative splicing is linked to thyroid tumorigenesis, we used our prediction database to select targets for analysis. Fifteen putatively new alternative splicing isoforms were selected on the basis of their expression in thyroid libraries and/or their origin in genes previously associated with carcinogenesis. Using a set of 66 normal, benign, and malignant thyroid tissue samples, new splicing events were confirmed by RT-PCR for 13 of IS genes (a validation rate of 87%). In addition, new alternative splicing isoforms not predicted by the system and not previously described in public databases were identified. Five genes (PTPN18, AB13BP, PFDN5, SULF2, and ST5) presented new and/or additional unpredicted isoforms differentially expressed between malignant and benign or normal thyroid tissues, confirmed by sequencing. PTPN18, AB13BP and PFDN5 revealed a statistically significant differential splicing profile. In addition, real-time PCR analysis revealed that expression of an alternative PFDN5 variant was higher in malignant lesions than in benign lesions or normal tissues. (c) 2006 Wiley-Liss, Inc.