EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

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Science  04 Jun 2004:
Vol. 304, Issue 5676, pp. 1497-1500
DOI: 10.1126/science.1099314
  • Fig. 1.

    Sequence alignment of selected regions within the EGFR and B-Raf kinase domains. Depiction of each type of EGFR mutation in human NSCLC. EGFR (gb:X00588) mutations in NSCLC tumors are highlighted in yellow. B-Raf (gb:M95712) mutations in multiple tumor types (5) are highlighted in blue. Asterisks denote residues conserved between EGFR and B-Raf. (A) L858R mutations in activation loop. (B) G719S mutant in P-loop. (C) Deletion mutants in EGFR exon 19.

  • Fig. 2.

    Positions of missense mutations G719S and L858R and the Del-1 deletion in the three-dimensional structure of the EGFR kinase domain. The activation loop is shown in yellow, the P-loop is in blue, and the C-lobe and N-lobe are as indicated. The residues targeted by mutation or deletion are highlighted in red. The Del-1 mutation targets the residues ELREA in codons 746 to 750.

  • Fig. 3.

    A lung adenocarcinoma cell line with EGFR receptor mutation is sensitive to growth and signaling inhibition by gefitinib. (A) Cells were treated with gefitinib at the indicated concentrations, and viable cells were measured after 72 hours of treatment. Percentage of cell growth is shown relative to untreated controls. H3255 cells have the EGFR L858R mutation, whereas the three remaining cell lines have wild-type EGFR (WT). (B) Inhibition of EGFR phosphorylation and of downstream phosphorylation of Akt and Erk1/2. The cell lines were treated with gefitinib for 24 hours. Cell extracts were immunoblotted to detect the indicated protein species. Akt, v-akt murine thymoma viral oncogene homolog; Erk, extracellular signal-responsive kinase.

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  • Abstract
    Full Text
    EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
    J. Guillermo Paez, Pasi A. Jänne, Jeffrey C. Lee, Sean Tracy, Heidi Greulich, Stacey Gabriel, Paula Herman, Frederic J. Kaye, Neal Lindeman, Titus J. Boggon, Katsuhiko Naoki, Hidefumi Sasaki, Yoshitaka Fujii, Michael J. Eck, William R. Sellers, Bruce E. Johnson, Matthew Meyerson

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    Materials and Methods
    Fig. S1
    Tables S1 to S4

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