A novel EGFR mutation D1012H and polymorphism at exon 25 in Japanese lung cancer

Mutations of the epidermal growth factor receptor (EGFR) gene at kinase domain have been reported in non-small-cell lung cancer (NSCLC). However, EGFR mutations status at C-terminal domain has not been reported in detail.We investigated the EGFR mutation and polymorphism statuses at C-terminal domain in 398 surgically treated NSCLC cases. Two hundred and sixty-eight adenocarcinoma cases were included. The presence or absence of EGFR mutation and polymorphism was analyzed by direct sequences.A novel EGFR somatic mutation at exon 25 (G3034, D1012H) was found from 1 of 398 lung cancer patients. During sequencing of EGFR C-terminal domain in NSCLC, 194 EGFR polymorphism (C2982T) cases were identified at exon 25. The polymorphism statuses were not correlated with gender, smoking status (never smoker vs. smoker), pathological subtypes and EGFR mutations. The EGFR polymorphism ratio was significantly higher in younger NSCLC (or =60, 56.8%) than in older NSCLC (60, 45.6%, P = 0.0467). The EGFR polymorphism ratio was significantly higher in lymph node positive NSCLC (57.4%) than in lymph node negative NSCLC (44%, P = 0.0168). In 46 total gefitinib treated NSCLC patients, exon 25 polymorphism was not correlated with prognosis.EGFR mutation at C-terminal in lung cancers seemed to be extremely rare, however, this D1012H mutation might be a role in EGFR function. EGFR polymorphism at exon 25 might be correlated with progression of NSCLC.