title: A novel point mutation in exon 20 of EGFR showed sensitivity to erlotinib.
abstract: Mutations of epidermal growth factor receptor (EGFR) gene are good predictors of response to treatment with EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC). It is well established that classic mutations, such as in-frame deletions in exon 19 and the point mutation L858R in exon 21, are associated with high sensitivity to EGFR TKIs. Though mutations in exon 20 are almost correlated with EGFR-TKIs resistance, the awareness that they might confer sensitivity to TKI treatment should be emphasized. Herein, we describe a novel mutation in exon 20 of EGFR in a Chinese male non-smoker, who was diagnosed with stage IV lung adenocarcinoma and characterized by the codon 769 point mutation GTG>GCG, which translates into alanine instead of valine (p.V769A). In this case, the patient showed a good clinical response to erlotinib after paclitaxel/cisplatin first-line and docetaxel second-line chemotherapies. Therefore, we suggest that this rare mutation (p.V769A) may be a sensitive EGFR mutation in NSCLC. The identification of novel EGFR mutations provides new predictive biomarkers for TKI treatment and is essential to the successful use of targeted therapies.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Xing
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zhao
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Luo
authors.forename: Huijie
authors.initials: H
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Jialei
authors.initials: J
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chang
authors.forename: Xianghua
authors.initials: X
authors.lastname: Wu
authors.forename: Aiqun
authors.initials: A
authors.lastname: Hu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage; D003062:Codon; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003062:Codon; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin