Cancer Research ：最新资料库—400个癌细胞系基因突变
新加坡与德国的科研人员经过三年努力之后，设立资料库，记录400个癌症细胞系的基因突变，为全球癌症研究员提供宝贵的资料。
新加坡科技研究局（新*科研）属下的生物医药研究院、生物细胞研究院和生物资讯研究院，以及德国马克斯·普朗克生物化学研究所(Max Planck Institute of Biochemistry)完成了一项重大的癌症细胞基因分析，并且将400个癌症细胞系出现的蛋白质酪氨酸激酶（protein tyrosine kinase）突变的数据，收录在名为“TYKIVA”的网上资料库。
由癌症研究专家尔里希教授（Axel Ullrich）率领的研究小组，在最新一期的《癌症研究》期刊，公布了资料库的细节。
蛋白质酪氨酸激酶是细胞内的蛋白质，在细胞生成和活动扮演重要的角色。研究发现蛋白质酪氨酸激酶的缺陷，与癌细胞病变息息相关。自1990年代，科研人员研究应付蛋白质酪氨酸激酶病变的药物，研制出副作用较少、比较有针对性的癌症药物。
新*科研发表文告宣布这项消息时说，TYKIVA网上资料库的设立，将能协助科研人员更好地了解癌细胞的分子基因和细胞结构，研制治疗癌症的药物。（联合早报）
原始出处:
Cancer Research 67, 11368-11376, December 1, 2007. doi: 10.1158/0008-5472.CAN-07-2703
Experimental Therapeutics, Molecular Targets, and Chemical Biology
Genetic Alterations in the Tyrosine Kinase Transcriptome of Human Cancer Cell Lines
Jens E. Ruhe1, Sylvia Streit1, Stefan Hart1, Chee-Hong Wong2, Katja Specht4, Pjotr Knyazev5, Tatjana Knyazeva5, Liang Seah Tay1, Hooi Linn Loo1, Priscilla Foo1, Winnie Wong1, Sharon Pok1, Shu Jing Lim1, Huimin Ong1, Ming Luo3, Han Kiat Ho1, Kaitian Peng1, Tze Chuen Lee2, Martin Bezler5, Christian Mann5, Silvia Gaertner5, Heinz Hoefler4, Stefano Iacobelli6, Stephan Peter7, Alice Tay3, Sydney Brenner1,3, Byrappa Venkatesh3 and Axel Ullrich1,5
1 Institute of Medical Biology, 2 Bioinformatics Institute, and 3 Institute of Molecular and Cell Biology, Singapore, Singapore; 4 Department of Pathology, Technical University of Munich, Munich, Germany; 5 Max-Planck-Institute for Biochemistry, Martinsried, Germany; 6 Department of Oncology, University of Chieti Medical School, Chieti, Italy; and 7 Department of Urology, Klinikum Darmstadt, Darmstadt, Germany
Requests for reprints: Jens E. Ruhe, U3 Pharma AG, Bunsenstrasse 1, 82152 Martinsried, Germany. E-mail: ruhe@u3pharma.com .
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. [Cancer Res 2007;67(23):11368–76]
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