Abstract
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.
Highlights
Research on established cancer cell lines has been the basis of pioneering discoveries in diverse areas of modern biology
For 254 established tumor cell lines of 19 tissue origins, we determined the profiles of both somatic mutations and germ line polymorphisms detectable in the transcripts of 90 Protein tyrosine kinases (PTKs) genes [15]
To comprehensively characterize widely used tumor cell lines with regard to nonsilent alterations in all expressed tyrosine kinase genes, we evaluated the sequence of the entire tyrosine kinase transcriptome (TKT) of 254 established cancer cell lines (Supplementary Table S1)
Summary
Research on established cancer cell lines has been the basis of pioneering discoveries in diverse areas of modern biology. For 254 established tumor cell lines of 19 tissue origins, we determined the profiles of both somatic mutations and germ line polymorphisms detectable in the transcripts of 90 PTK genes [15].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
