title: Epidermal growth factor receptor extracellular domain mutations in primary glioblastoma.
abstract: OBJECTIVE
  Novel missense mutations of the epidermal growth factor receptor (EGFR) extracellular domain have been recently described in a large series of glioblastomas.
  
  
  METHODS
  The exons 2, 3, 7, 8 and 15 coding for the EGFR extracellular domain were sequenced in a series of 161 consecutive primary glioblastomas and correlated with clinical features of patients in order to determine whether these alterations are linked to specific clinical characteristics of the disease.
  
  
  RESULTS
  Missense mutations were observed in 18 cases (11.2%), and 4 novel mutations were detected, including G178C, A271C, C818A and C1860G. Mutations of the EGFR extracellular domain were not associated with overall survival or with age at onset of the disease. In contrast, the EGFR extracellular domain mutations were significantly associated with patients' gender. Indeed, 15 mutations were observed in men vs. 3 in women (P < 0.05). EGFR extracellular domain mutations were also strongly associated with EGFR amplification (P < 0.0001).
  
  
  CONCLUSIONS
  To our knowledge, EGFR extracellular domain mutations are the first genomic abnormalities associated with gender in primary glioblastomas, although a link between mutations of the EGFR tyrosine kinase domain and gender has been previously made in lung cancer.
authors.affiliation: INSERM, Unité 711, Paris, France. ahmed.idbaih@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Idbaih
authors.forename: J
authors.initials: J
authors.lastname: Aimard
authors.forename: B
authors.initials: B
authors.lastname: Boisselier
authors.forename: Y
authors.initials: Y
authors.lastname: Marie
authors.forename: S
authors.initials: S
authors.lastname: Paris
authors.forename: E
authors.initials: E
authors.lastname: Crinière
authors.forename: R
authors.initials: R
authors.lastname: Carvalho Silva
authors.forename: F
authors.initials: F
authors.lastname: Laigle-Donadey
authors.forename: A
authors.initials: A
authors.lastname: Rousseau
authors.forename: K
authors.initials: K
authors.lastname: Mokhtari
authors.forename: J
authors.initials: J
authors.lastname: Thillet
authors.forename: M
authors.initials: M
authors.lastname: Sanson
authors.forename: K
authors.initials: K
authors.lastname: Hoang-Xuan
authors.forename: J-Y
authors.initials: JY
authors.lastname: Delattre
mesh_terms: D017668:Age of Onset; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012727:Sex Characteristics
chemical_list: D066246:ErbB Receptors