Evidence that public database records for many cancer-associated genes reflect a splice form found in tumors and lack normal splice forms.
Evidence that public database records for many cancer-associated genes reflect a splice form found in tumors and lack normal splice forms.
复制标题
DOI：
10.1093/nar/gki792
复制
发表时间：
2005
影响因子：
14.9
通讯作者：
Lee, C
中科院分区：
文献类型：
--
作者：
Roy, M;Xu, Q;Lee, C
选择性剪接在人类基因组中广泛存在，而且似乎许多基因在癌症组织中表现出不同于正常人类组织中的剪接形式。然而，由于许多癌症相关基因的cDNA最初是从肿瘤样本中克隆出来的，因此重要的是要问，这个cDNA谱库是否提供了正常组织中发现的转录异构体的完整或具有代表性的图景。为了回答这个问题，我们使用生物信息学和RT-PCR来识别新的剪接形式，重点是框内外显子跳跃，在正常组织样本中的一组50个癌症相关基因。这些数据表明，在近三分之二的基因中，正常组织表达以前未知的剪接形式，其中40%通常是显性剪接形式。令人惊讶的是，肿瘤相关剪接形式在GenBank中出现的可能性是正常组织相关剪接形式的两倍，最可能的原因是GenBank中这些基因的70%的mRNAs是从肿瘤样本中克隆的。作为一个例子，我们描述了一种新的正常剪接形式的IkBβ，它是NFκB途径的重要调节因子。我们的数据表明，系统地重新评估正常组织中癌症基因的剪接形式将有助于深入了解它们在正常组织和癌症中的不同功能。我们的数据库包含1308种新的正常剪接形式，包括许多已知的癌症基因。
Alternative splicing is widespread in the human genome, and it appears that many genes display different splice forms in cancerous tissue than in normal human tissues. However, since cDNAs for many cancer-associated genes were originally cloned from tumor samples, it is important to ask whether this repertoire of cDNAs provides a complete or representative picture of the transcript isoforms found in normal tissues. To answer this, we used bioinformatics and RT–PCR to identify novel splice forms, focusing on in-frame exonskips, for a panel of 50 cancer-associated genes in normal tissue samples. These data show that in nearly two-thirds of the genes, normal tissues expressed previously unknown splice forms, of which 40% were normally a dominant splice form. Surprisingly, the tumor-associated splice forms were twice as likely to be represented in GenBank than their normal tissue-associated splice forms, most likely because 70% of the mRNAs in GenBank for these genes were cloned from tumor samples. As an example, we describe a novel normal splice form of IKBβ, an important regulator of the NFκB pathway. Our data suggest that systematic re-evaluation of cancer genes' splice forms in normal tissue will yield insights into their distinct functions in normal tissues and in cancer. Our database contains 1308 novel normal splice forms, including many known cancer genes.
登录
查看更多内容
影响因子：
11.4
作者：
Strausberg, RL;Buetow, KH;Klausner, RD
通讯作者：
Klausner, RD
影响因子：
14.9
作者：
Modrek, B;Resch, A;Lee, C
通讯作者：
Lee, C
影响因子：
14.9
作者：
Lee, C;Atanelov, L;Xing, Y
通讯作者：
Xing, Y
影响因子：
8
作者：
Hui, LJ;Zhang, X;Hu, GX
通讯作者：
Hu, GX
DOI：
10.1073/pnas.0136770100
发表时间：
2003-01-07
影响因子：
11.1
作者：
Lewis, BP;Green, RE;Brenner, SE
通讯作者：
Brenner, SE