title: EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients.
abstract: To determine whether EGFR tyrosine kinase domain mutations are early events in the pathogenesis of lung adenocarcinomas, we tested for the presence of EGFR mutations in histologically normal bronchial and bronchiolar epithelia from lung adenocarcinomas bearing the common EGFR mutations. DNA was extracted from microdissected tissue obtained from 21 tumors with known EGFR mutations, 16 tumors without mutation, and 90 sites of normal bronchial and bronchiolar epithelium from the same surgical specimens. With the use of PCR and direct DNA sequencing, EGFR mutations identical to the tumors were detected in the normal respiratory epithelium in 9 of 21 (43%) patients with EGFR mutant adenocarcinomas but none in patients without mutation in the tumors. The finding of mutations being more frequent in normal epithelium within tumor (43%) than in adjacent sites (24%) suggests a localized field effect phenomenon. Our findings indicate that mutation of the tyrosine kinase domain of EGFR is an early event in the pathogenesis of lung adenocarcinomas, and suggest EGFR mutations as an early detection marker and chemoprevention target.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
authors.forename: Ximing
authors.initials: X
authors.lastname: Tang
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001980:Bronchi / Q000201:enzymology / Q000502:physiology; D004847:Epithelial Cells / Q000201:enzymology / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary
chemical_list: D066246:ErbB Receptors