title: A dramatic lung cancer course in a patient with a rare EGFR germline mutation exon 21 V843I: Is EGFR TKI resistance predictable?
abstract: We report on the medical history of a Caucasian smoker woman diagnosed with a stage IV NSCLC adenocarcinoma, characterized by a rare epidermal growth factor receptor (EGFR) point mutation in exon 21 codon 843 (p.V843I/c.2527G>A/COSMIC ID 85894). This genetic alteration revealed to be germline, after its presence was demonstrated in chondroblasts from the bone biopsy. While it is the first description of germline V843I mutation without concomitant additional known EGFR activating mutation, we modeled the EGFR ATP catalytic domain in complex with ATP, gefitinib and erlotinib using computer-aided approaches to estimate possible changes in affinity upon the V843I mutation.
authors: HFR Fribourg, Hôpital Cantonal, Department of Internal Medicine, Division of Oncology, Fribourg, Switzerland.
authors: Nadine
authors: N
authors: Demierre
authors: Vincent
authors: V
authors: Zoete
authors: Olivier
authors: O
authors: Michielin
authors: Edouard
authors: E
authors: Stauffer
authors: Dieter R
authors: DR
authors: Zimmermann
authors: Daniel C
authors: DC
authors: Betticher
authors: Solange
authors: S
authors: Peters
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors