title: High proportion of rare and compound epidermal growth factor receptor mutations in an Australian population of non-squamous non-small-cell lung cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation positivity in primary non-small-cell lung cancer (NSCLC) may confer increased sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy with improved progression-free survival over EGFR wild-type tumours. Some mutation subtypes may not confer such TKI sensitivity. The incidence of rare and compound subtypes in the Australian lung cancer population is not fully defined.
  
  
  OBJECTIVE
  The aim of the study was to audit the incidence of EGFR mutation in serial cases of primary non-squamous NSCLC presenting to two multidisciplinary team meetings in metropolitan Sydney for incidence, type of mutation and phenotypic association with mutation positivity.
  
  
  METHODS
  Serially presenting cases of primary non-squamous NSCLC were tested for EGFR mutation. The cases presented to either of two multidisciplinary team meetings in metropolitan Sydney and were referred for EGFR mutation testing on the basis of non-squamous NSCLC histopathology. Samples from the two sites were analysed for EGFR mutation at one of three different laboratories, each using a slightly different assay. Data on phenotypic characteristics, smoking history and clinicopathological features of the tumour were collected.
  
  
  RESULTS
  There is a relatively high incidence of EGFR mutation in non-squamous NSCLC in a series of patients drawn from two metropolitan multidisciplinary team meetings in Sydney at a rate of 23.8%. A high proportion of rare and compound EGFR mutations were identified (6/32 mutation positive cases, 18.8%).
  
  
  CONCLUSIONS
  The incidence of EGFR mutation may be higher in Australian populations than in other populations of predominantly European origin. Rare and compound EGFR mutations may occur and may have implications for treatment that differ from classically activating mutations.
authors.affiliation: St Vincent's Hospital Sydney, Sydney, New South Wales, Australia; Kinghorn Cancer Centre, Sydney, New South Wales, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Stone
authors.forename: H A
authors.initials: HA
authors.lastname: Allen
authors.forename: T
authors.initials: T
authors.lastname: Saghaie
authors.forename: A
authors.initials: A
authors.lastname: Abbott
authors.forename: R
authors.initials: R
authors.lastname: Daniel
authors.forename: R S
authors.initials: RS
authors.lastname: Mead
authors.forename: M
authors.initials: M
authors.lastname: Kohonen-Corish
authors.forename: M
authors.initials: M
authors.lastname: Plit
authors.forename: L
authors.initials: L
authors.lastname: Morgan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001315:Australia / Q000453:epidemiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: DNA sequence analysis; epidermal growth factor receptor; epidermal growth factor/antagonist and inhibitor; mutation; non-small-cell lung cancer; receptor