Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines.
Genetic alterations in the tyrosine kinase transcriptome of human cancer cell lines.
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DOI：
10.1158/0008-5472.can-07-2703
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发表时间：
2007-12
期刊：
影响因子：
11.2
通讯作者：
J. Ruhe;S. Streit;S. Hart;Chee‐Hong Wong;K. Specht;P. Knyazev;T. Knyazeva;L. Tay;Hooi Linn Loo;P. Foo;Winnie Wong;S. Pok;S. Lim;H. Ong;Ming Luo;H. Ho;Kaitian Peng;Tze-Chuen Lee;M. Bezler;C. Mann;Silvia Gaertner;H. Hoefler;S. Iacobelli;S. Peter;Alice Tay;S. Brenner;B. Venkatesh;A. Ullrich
中科院分区：
文献类型：
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作者：
J. Ruhe;S. Streit;S. Hart;Chee‐Hong Wong;K. Specht;P. Knyazev;T. Knyazeva;L. Tay;Hooi Linn Loo;P. Foo;Winnie Wong;S. Pok;S. Lim;H. Ong;Ming Luo;H. Ho;Kaitian Peng;Tze-Chuen Lee;M. Bezler;C. Mann;Silvia Gaertner;H. Hoefler;S. Iacobelli;S. Peter;Alice Tay;S. Brenner;B. Venkatesh;A. Ullrich
蛋白酪氨酸激酶（Protein tyrosine kinases，PTKs）在肿瘤细胞特性的表现中起着关键作用，其信号传导机制已在永生化肿瘤细胞中得到广泛研究。为了表征和分析常用的癌细胞系中所有表达的PTK的一级结构的变化，我们对254个已建立的肿瘤细胞系的整个酪氨酸激酶转录组进行了基于cDNA的序列分析。细胞系内在PTK转录物改变的概况和155个鉴定的多态性和234个体细胞突变的评价可在命名为“Tykiva”（酪氨酸激酶组变体）的数据库中获得。组织分布分析和/或在定义的蛋白质结构域内的定位表明几种遗传改变的功能相关性。例如，成纤维细胞生长因子受体4中高度保守的Y367残基的半胱氨酸替换或肿瘤抑制激酶CSK中的Q26 X无义突变，可能有助于细胞系特异性信号传导特征和肿瘤进展。此外，已知的变体，如表皮生长因子受体G719 S，被证明介导抗癌药物敏感性，可以检测到其他比以前报道的肿瘤类型。因此，我们的数据为基于细胞系的癌症研究的设计和解释提供了广泛的系统信息，并可能刺激对当前癌症治疗的更广泛临床应用的进一步研究。
Protein tyrosine kinases (PTKs) play a critical role in the manifestation of cancer cell properties, and respective signaling mechanisms have been studied extensively on immortalized tumor cells. To characterize and analyze commonly used cancer cell lines with regard to variations in the primary structure of all expressed PTKs, we conducted a cDNA-based sequence analysis of the entire tyrosine kinase transcriptome of 254 established tumor cell lines. The profiles of cell line intrinsic PTK transcript alterations and the evaluation of 155 identified polymorphisms and 234 somatic mutations are made available in a database designated "Tykiva" (tyrosine kinome variant). Tissue distribution analysis and/or the localization within defined protein domains indicate functional relevance of several genetic alterations. The cysteine replacement of the highly conserved Y367 residue in fibroblast growth factor receptor 4 or the Q26X nonsense mutation in the tumor-suppressor kinase CSK are examples, and may contribute to cell line-specific signaling characteristics and tumor progression. Moreover, known variants, such as epidermal growth factor receptor G719S, that were shown to mediate anticancer drug sensitivity could be detected in other than the previously reported tumor types. Our data therefore provide extensive system information for the design and interpretation of cell line-based cancer research, and may stimulate further investigations into broader clinical applications of current cancer therapeutics.