EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients

Ximing Tang, Hisayuki Shigematsu, B. Nebiyou Bekele, Jack A. Roth, John D. Minna, Waun Ki Hong, Adi F. Gazdar, Ignacio I. Wistuba

Research output: Contribution to journalArticlepeer-review

214 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7568-7572
Number of pages5
JournalCancer research
Volume65
Issue number17
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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