molecular modeling and description of a newly characterized activating mutation of the egfr gene in non-small cell lung cancer分子建模和描述的一个新特征激活表皮生长因子受体基因突变在非小细胞肺癌.pdfVIP

Otto et al. Diagnostic Pathology 2012, 7:146 /content/7/1/146 SHORT REPORT Open Access Molecular modeling and description of a newly characterized activating mutation of the EGFR gene in non-small cell lung cancer * Claudia Otto, Agnes Csanadi, Paul Fisch, Martin Werner and Gian Kayser Abstract: Lung cancer is the leading cause of death among malignant diseases in humans worldwide. In the last decade development of new targeted drugs for the treatment of non-small cell lung cancer proved to be a promising approach to prolong the otherwise very poor prognosis of patients with advanced UICC stages. Epidermal growth factor receptor (EGFR) has been in the focus of this lung cancer science and specific activating mutations are eligible for the treatment with specific tyrosine kinase inhibitors like gefitinib or erlotinib. Beside typical deletions in exon 19 and point mutations in exons 18 and 21 several insertions in exon 19 have been described and attributed activating properties as well. This is the first European and overall the 5th description in English literature of one of these specific insertions. To elucidate its structural changes leading to the activating properties we performed molecular modeling studies. These revealed conformational and electrostatic force field changes in the kinase domain of EGFR. To not miss uncommon mutations thorough and precise characterization of EGFR hotspots, i. e. at least exons 18, 19 and 21, should therefore be conducted to provide best medical care and to offer lung cancer patients appropriate cancer treatment. Virtual slides: The vistual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/ 2209889658102062 Short report