Creation of an EGFR somatic mutation database (www.egfr-mutations.org)

Abstract

11111 Background: Following the discovery of somatic mutations in the tyrosine kinase domain (exons 18–24) of the epidermal growth factor receptor (EGFR) correlating with dramatic responses of non-small cell lung cancer (NSCLC) to the tyrosine kinase inhibitors gefitinib and erlotinib (TKIs), there has been increasing interest in utilizing this molecular marker for treatment selection. We aimed to analytically catalogue the mutational spectrum of somatic mutations in EGFR and correlate specific mutations with clinico-pathological factors and TKI efficacy. Methods: A computerized search of the PubMed database (01/Jan/04 - 30/June/07) was performed to identify published articles dealing with the identification of somatic mutations in EGFR pertaining to NSCLC. Only peer-reviewed articles were considered eligible. Demographic, clinico-pathological, mutational and efficacy data were abstracted. Results: From a total of 202 articles, we abstracted data on 12,244 patients with 3,381 somatic EGFR mutations. The mutational spectrum ranged across the 186 amino acids of exons 18–21, with 109 (58.6%) being associated with a somatic mutation. The majority of mutations have been reported on only one occasion (158 of 254, 62.2%), with only 9 different mutations occurring at a rate of ≥1%. The two most common mutations, L858R and delE746-A750 account for 32.84% and 24.28% of all mutations respectively. Deletions’ and ‘deletional-insertions’ in Exon 19 alone account for 47.35%. Although a meta-analysis of all articles was considered inappropriate, there was a clear association between the presence of mutations and response to TKIs. The dataset also highlighted the correlation of mutations with the accepted clinico-pathological factors (gender, histology, ethnicity and smoking status). Conclusions: We have generated a free-access online analytical database of somatic EGFR mutations in NSCLC. Cumulative information will be made available through a routine update of both database tables and associated graphical representations. Updates and submissions directly through the online site (www.egfr-mutations.org) are encouraged, as are comments and suggestions. The first 6-month update of the database will be presented at the meeting. No significant financial relationships to disclose.