Analysis of EGFR, EML4-ALK, KRAS, and c-MET mutations in Chinese lung adenocarcinoma patients

Exp Lung Res. 2013 Oct;39(8):328-35. doi: 10.3109/01902148.2013.819535. Epub 2013 Aug 6.

Abstract

Introduction: Mutation analysis of cancer driver genes is helpful for determining an optimal treatment strategy. We evaluated mutations in four driver genes, namely epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients from Hunan Province.

Methods: We enrolled 110 lung adenocarcinoma patients in a single institution. EGFR and KRAS mutations were examined by direct sequencing, the EML4-ALK fusion gene was analyzed by fluorescence in situ hybridization, and c-MET amplification and c-Met protein expression were detected by quantitative PCR and immunohistochemistry, respectively.

Results: EGFR and KRAS mutations were observed in 52.7% (58/110) and 3.6% (4/106) of patients, respectively. c-MET amplification was detected in 5.5% (6/110) of patients. In addition, 30% (33/110) of the cases expressed c-Met protein, including all of the patients harboring c-MET amplification. Ten percent (11/110) of patients harbored the EML4-ALK fusion gene, and the frequency of ALK rearrangement was higher than that of other cohort analyses involving patients from other regions in China. Almost all of these gene mutations were exclusive except that in two female non-smoking patients, who harbored an EGFR mutation and EML4-ALK rearrangement simultaneously. In total, 70% of patients in the study harbored one of the four gene mutations.

Conclusions: Most Chinese lung adenocarcinoma patients harbor driver gene mutations, among which ALK rearrangements were more common in Hunan patients than in previously reported populations. Future clinical trials should be conducted to determine the safety and efficacy of drug combination targeting different driver mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / therapy
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • China
  • DNA Mutational Analysis
  • ErbB Receptors / genetics
  • Female
  • Gene Amplification
  • Genes, erbB-1*
  • Genes, ras
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation*
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / genetics*

Substances

  • EML4-ALK fusion protein, human
  • KRAS protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • EGFR protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins