title: Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy.
abstract: BACKGROUND
  The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned.
  
  
  METHODS
  We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR.
  
  
  RESULTS
  Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC.
  
  
  CONCLUSIONS
  Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.
authors.affiliation: Tumorzentrum, Luzerner Kantonsspital, Lucerne, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.forename: Carola
authors.initials: C
authors.lastname: Stadelmann
authors.forename: Franziska
authors.initials: F
authors.lastname: Aebersold-Keller
authors.forename: Katharina
authors.initials: K
authors.lastname: König
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Heukamp
authors.forename: Daniel
authors.initials: D
authors.lastname: Betticher
authors.forename: Christa
authors.initials: C
authors.lastname: Baumann
authors.forename: Katharina
authors.initials: K
authors.lastname: Buser
authors.forename: Antonello
authors.initials: A
authors.lastname: Calderoni
authors.forename: Adrian
authors.initials: A
authors.lastname: Casty
authors.forename: Giannicola
authors.initials: G
authors.lastname: DʼAddario
authors.forename: Claudius
authors.initials: C
authors.lastname: Irlé
authors.forename: Christoph
authors.initials: C
authors.lastname: Mamot
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morant
authors.forename: Andreas
authors.initials: A
authors.lastname: Trojan
authors.forename: Erica
authors.initials: E
authors.lastname: Pellicioli
authors.forename: Sonja
authors.initials: S
authors.lastname: Jehle-Schwertfeger
authors.forename: Stefan
authors.initials: S
authors.lastname: Aebi
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015995:Prevalence; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D012907:Smoking / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib