Supplementary Materials

Supplementary Material for:

Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer

Hiroyuki Yasuda, Eunyoung Park, Cai-Hong Yun, Natasha J. Sng, Antonio R. Lucena-Araujo, Wee-Lee Yeo, Mark S. Huberman, David W. Cohen, Sohei Nakayama, Kota Ishioka, Norihiro Yamaguchi, Megan Hanna, Geoffrey R. Oxnard, Christopher S. Lathan, Teresa Moran, Lecia V. Sequist, Jamie E. Chaft, Gregory J. Riely, Maria E. Arcila, Ross A. Soo, Matthew Meyerson, Michael J. Eck,* Susumu S. Kobayashi,* Daniel B. Costa*

*Corresponding author. E-mail: dbcosta{at}bidmc.harvard.edu (D.B.C.); skobayas{at}bidmc.harvard.edu (S.S.K.); eck{at}red.dfci.harvard.edu (M.J.E.)

Published 18 December 2013, Sci. Transl. Med. 5, 216ra177 (2013)
DOI: 10.1126/scitranslmed.3007205

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Transforming ability of EGFR mutant constructs introduced into Ba/F3 cells.
  • Fig. S2. EGFR mutant constructs introduced into Cos-7 cells.
  • Fig. S3. Determination of the Michaelis constant for ATP (Km[ATP]) for EGFR mutants.
  • Fig. S4. Inhibition of EGFR mutant kinases by gefitinib at a range of ATP concentrations.
  • Fig. S5. Examples of computed tomography (CT) images of patients with NSCLC harboring EGFR exon 20 insertion mutations.
  • Fig. S6. Kaplan-Meier progression-free survival (PFS) curve estimates.
  • Fig. S7. Pathology from a never smoker with an adenocarcinoma of the lung harboring EGFR A763_Y764insFQEA.
  • Fig. S8. Different morphologic features of EGFR-mutated NSCLC cell lines.
  • Fig. S9. Copy number changes in BID007.
  • Fig. S10. Additional implications of the crystal structure of the prototypical post–C helix EGFR exon 20 insertion D770_N771insNPG (insNPG).
  • Fig. S11. Size-exclusion chromatography of EGFR exon 20 insertion kinase domains.
  • Table S1. Amino acid sequence of EGFR exon 20 insertion mutations designed for in vitro studies.
  • Table S2. Summary of IC50s obtained with different EGFR mutations.
  • Table S3. Clinical, pathological, and molecular characteristics and response to reversible EGFR TKIs for patients with tumors harboring EGFR exon 20 insertions.
  • Table S4. Genes analyzed for hotspot mutations using OncoMap version 3 extended analysis.
  • Table S5. Crystallographic data collection and refinement statistics for EGFRD770_N771insNPG and EGFR-L858R bound to the irreversible EGFR TKI PD168393.
  • Table S6. Oligonucleotides used to derive EGFR exon 20 insertion mutations.
  • References (63–70)

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