title: Molecular modeling and description of a newly characterized activating mutation of the EGFR gene in non-small cell lung cancer.
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.
  The vistual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2209889658102062.
authors.affiliation: Institute of Pathology, University Medical Center Freiburg, Breisacher Strasse 115a, D-79106, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Otto
authors.forename: Agnes
authors.initials: A
authors.lastname: Csanadi
authors.forename: Paul
authors.initials: P
authors.lastname: Fisch
authors.forename: Martin
authors.initials: M
authors.lastname: Werner
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008958:Models, Molecular; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000032:analysis; D010641:Phenotype; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C512478:EGFR protein, human; D066246:ErbB Receptors