Spectrum of EGFR mutations associated with non-small cell lung cancer in an Asian Chinese population
20055 Background: Somatic mutations in tyrosine kinase (TK) domain of the EGFR gene, predicting for sensitivity to TK inhibition therapy, are over-represented in lung cancer with adenocarcinoma or bronchioloalveolar histology, non-smokers, female gender and East Asian ethnicity. Methods: We prospectively screened for EGFR mutations at exons 19–21 on micro-dissected specimen enriched for tumor cells by direct nucleotide sequencing in Hong Kong Chinese patients. Results: From May 2005 onwards, a total of 27 patients were analyzed. They comprised 11 males and 16 females with a median age of 67 years. Histological diagnoses were adenocarcinoma (n = 22), bronchioloalveolar carcinoma (n = 4) and squamous cell carcinoma (n = 1). Samples included primary tumor (n = 20) as well as metastatic lesions (n = 7). EGFR mutations were detected in 17 patients (63%), the most common being L858R at exon 21 (n = 7) followed by exon 19 deletions (del(746–750) = 3, del(747–751) = 1, del(747–753) = 3) and G719C at exon 18 (n = 1). Two patients showed novel EGFR mutations, namely 4-base pair insertion deletion at exon 19 leading to substitution of Glu746-Leu747 by Val746-Pro747 and three base pair deletion at exon 18 leading to replacement of Glu709-Thr710 by Asp. Furthermore, two patients showed double mutations, including novel S768I at exon 20 in combination with G719C, and novel K860I at exon 21 in combination with L858R. Finally, one patient showed homozygous del(747–753) as detected by sequencing in both primary lung tumor and brain secondary, which might represent loss of heterozygosity. Conclusions: Similar to other series, two hotspots i.e. exon 19 deletion and L858 account for the majority (82%) of detectable EGFR mutations in our patient population. For the rare and novel variants, it would be of interest to document the clinical responsiveness to TK inhibitors gefitinib and erlotinib, so that a more complete picture of cancer genotype phenotype correlation can be achieved. No significant financial relationships to disclose.