Abstract 4158: Identification of somatic mutations inEGFR/KRAS/ALK-negative lung adenocarcinoma from never smokers

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Lung adenocarcinoma is a highly heterogeneous disease with various etiologies, prognoses, and responses to therapy. Although genome-scale characterization of lung adenocarcinoma has been performed, somatic mutation analysis of never-smoker EGFR/KRAS/ALK-negative lung adenocarcinoma has not been comprehensively conducted. Methods: Patients with lung adenocarcinoma were eligible if they were never smoker without EGFR/KRAS mutation and ALK rearrangement. Whole exome sequencing was performed using the Illumina HiSeq 2,000 platform. Candidate loci identified in whole exome sequencing were validated using hybridization capture method and Sanger sequencing. Results: We present an analysis of whole exome sequencing data from 16 EGFR/KRAS/ALK-negative lung adenocarcinomas with additional 54 tumors in two independent cohort sets. We identified 27 genes potentially implicated in the pathogenesis of lung adenocarcinoma. In addition to targetable PI3K/mTOR signaling (TSC1, PIK3CA, AKT2) and receptor tyrosine kinase (RTK) signaling (ERBB4) genes, some of the genes including SETD2 and PBRM1 (chromatin remodeling), CHEK2 and CDC27 (cell cycle), CUL3 and SOD2 (oxidative stress), and CSMD3 and TFG (immune response) have not been previously highlighted in lung adenocarcinomas. In total (N=70), TP53 is the most frequently altered gene (11%), followed by SETD2 (6%), CSMD3 (6%), ERBB2 (6%), and CDH10 (4%). In pathway analysis, majority of altered genes were involved in cell cycle/DNA repair (P<0.001), and cAMP-mediated protein kinase A signaling (P<0.001). Conclusions: Genomic makeup of EGFR/KRAS/ALK-negative adenocarcinomas in never-smokers was remarkably diverse. Impairment in cell cycle/DNA repair may be involved in tumorigenesis and therapeutic targets in lung adenocarcinoma. Note: This abstract was not presented at the meeting. Citation Format: Han Sang Kim, Jin Woo Ahn, Jung-Ki Yoon, Soo Min Han, Hoon Jang, Sungho Eun, Hyo Sup Shim, Hyun Jung Kim, Dae Joon Kim, Jin Gu Lee, Chang Young Lee, Mi Kyung Bae, Kyung Young Chung, Eun Young Kim, Ji Ye Jung, Se Kyu Kim, Joon Chang, Hye Ryun Kim, Joo Hang Kim, Ji Hyun Lee, Duhee Bang, Byoung Chul Cho. Identification of somatic mutations in EGFR/KRAS/ALK -negative lung adenocarcinoma from never smokers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4158. doi:10.1158/1538-7445.AM2014-4158