MYC and EIF3H Coamplification significantly improve response and survival of non-small cell lung cancer patients (NSCLC) treated with gefitinib

J Thorac Oncol. 2009 Apr;4(4):472-8. doi: 10.1097/JTO.0b013e31819a5767.


Background: We investigated the incidence of eukaryotic translation initiation factor 3 subunit H (EIF3H) and MYC amplification in non-small cell lung cancer (NSCLC) patients, and whether MYC/EIF3H increased gene copy number affected response to Epidermal Growth Factor Receptor tyrosine kinase inhibitors.

Methods: Metastatic NSCLC patients (n = 54) treated with gefitinib were analyzed for the genomic content of EIF3H and MYC genes by fluorescence in situ hybridization (FISH) using a custom-designed 3-color DNA probe set.

Result: Amplification of EIF3H (ratio EIF3H/CEP8 >2), was observed in 10 cases (18.5%), and MYC was coamplified in all. MYC amplification without coamplification of EIF3H was observed in 2 cases (3.7%). Receiver operating characteristic analysis was conducted to identify the cutoff for MYC and EIF3H copy number best discriminating sensitive and resistant populations. MYC FISH positive patients (MYC+, mean > or =2.8) had a significantly higher response rate (p = 0.003), longer time to progression (p = 0.01) and overall survival (OS: p = 0.02) than MYC- (mean <2.8). Similarly, EIF3H FISH positive patients (EIF3H+, mean > or =2.75) had a significantly higher response rate (p = 0.002), longer time to progression (p = 0.01) and OS (p = 0.01) than EIF3H- (mean <2.75).

Conclusion: Our results indicate that MYC and EIF3H are frequently coamplified in NSCLC and that a high copy number correlates with increased epidermal growth factor receptor tyrosine kinase inhibitors sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Eukaryotic Initiation Factor-3 / genetics*
  • Female
  • Gefitinib
  • Gene Amplification*
  • Genes, myc*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*


  • Antineoplastic Agents
  • Eukaryotic Initiation Factor-3
  • Protein Kinase Inhibitors
  • Quinazolines
  • Gefitinib