Abstract 790: Mutations and copy number gains of EGFR and KRAS genes in lung adenocarcinomas

Abstract

Abstract Background: Activating mutations or copy number gains (CNGs) of epidermal growth factor receptor (EGFR) and KRAS genes are major oncogenic alterations in lung adenocarcinomas. While mutations of these genes are well-known to be mutually exclusive each other, the interrelationship of four genetic alterations (mutations or CNGs of EGFR or KRAS gene) has never been investigated. Material and methods: We determined these four genetic alterations in 314 lung adenocarcinoma cases including 176 Asians and 138 Non-Asians from four countries with complete clinical information. Mutational and CNG statuses of EGFR or KRAS gene were determined by direct sequencing and quantitative PCR method, respectively. Results: EGFR mutations (mEGFR), EGFR CNGs (gEGFR), KRAS mutations (mKRAS) and KRAS CNGs (gKRAS) were present in 25%, 35%, 23% and 6% of 314 cases, respectively (Table 1). Either alteration of EGFR or KRAS gene was present in 41% and 20% of all cases, respectively. Alterations of either EGFR or KRAS gene were observed in 67% of 314 cases, that was significantly more frequent in Asian never smokers (84%) than other groups (61%, P = 0.0001). Of note, CNGs of both genes preferentially occurred in their respective mutant case (P = 0.001 in EGFR and P = 0.04 in KRAS). mEGFR and mKRAS were completely mutually exclusive each other while gEGFR and gKRAS were not. Either alteration of EGFR was also exclusively present with either alteration of KRAS (P < 0.0001) while 19 cases (6%) had alterations of both genes. Interestingly, gKRAS was detected in one case among 79 mEGFR cases (1.3%) while gEGFR could be observed in 10 cases among 71 mKRAS cases (14.1%, P = 0.003). Conclusion: Activations of EGFR and/or KRAS genes are present in about 70% of lung adenocarcinomas. Activations of EGFR or KRAS gene are almost exclusive and activating mutation of EGFR rarely accompanies KRAS activation, suggesting that two genetic alterations independently associate with oncogenesis of lung adenocarcinomas.Table 1.Activated pathway of 314 lung adenocarcinomasActivated pathwayTypes of activationn%Both genesSubtotal196.1 m, gEGFR + gKRAS10.3 gEGFR + m, gKRAS51.6 gEGFR + mKRAS51.6 gEGFR + gKRAS82.5 EGFR gene aloneSubtotal12941.1 mEGFR3912.4 m, gEGFR3912.4 gEGFR5116.2 KRAS gene aloneSubtotal6219.7 mKRAS5818.5 m, gKRAS31.0 gKRAS10.3 NoneSubtotal10433.1 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 790.