Abstract 5343: Mutational signatures in EGFR sensitizing mutation positive lung adenocarcinoma

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Abstract Lung cancer has high mutational burden, which is featured by smoking signature. However, lung cancer with EGFR mutations is common in nonsmokers and women, which suggests that mutational stresses other than smoking are involved. We analyzed repeated deep sequencing data of EGFR sensitizing mutation positive lung adenocarcinoma tissue to identify characteristic mutational signatures, proposed by Alexandrov et al. Targeted next-generation sequencing was performed using Ion AmpliSeq Custom Panel of 0.6 Mb size containing 70 major genes including EGFR in 69 cases harboring sensitizing EGFR mutation. Publicly available data from EGFR sensitizing mutation were extracted from GDC data portal. Mutational signature was analyzed using maftools package. EGFR-TKI domain analysis revealed 53 mutations. C> T mutation was found in 26.4%, but C> T transition at CpG site that suggests aging effect was found in 2%, and C> T or C> G mutation in TCW motif reflecting APOBEC activity were found in 1.4%. C> A transversion corresponding to Signature 4 was also found in only one case, suggesting that the possibility of EGFR mutation by smoking effect is very low. The T> C substitution in ApT, indicating signature 5, was detected in 4%. The EGFR-TKI sensitizing mutation (E19del, L858R) has lower frequency of co-mutation while other EGFR-TKI domain mutations were frequently associated with multiple co-mutations. T>G substitution, indicating signature 28 and commonly found in Korean gastric cancer, was found in 39.1%. When the mutational signatures of a total 70 genes were analyzed, the C> T mutation was the most commonly detected (73.1%) and similarity with signature 5 was highest. These findings suggest that the mutational signature of EGFR sensitizing mutant lung cancer, which is frequent in Far East Asia, may be different from that of Western data. Additional data and analysis will be updated until the annual meeting. Citation Format: Eun Young Kim, Arum Kim, Yoon Soo Chang. Mutational signatures in EGFR sensitizing mutation positive lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5343.