The Identification And Characterization Of Genetic Variations In Lung Adenocarcinomas In A Japanese Population

Abstract Lung adenocarcinoma is a major histological subtype of non-small cell lung cancer. Previous studies have revealed substantial clinical and molecular differences between the Asian and Caucasian populations. Kinase inhibitor-sensitive EGFR mutations are frequently detected in Asian, female and non-smoker population. These findings suggest unique genetic and/or environmental background of carcinogenesis of this tumor. In the present study, we generated and analyzed a dataset of single-nucleotide variants (SNVs) and small insertions and deletions (indels) in the entire exon regions (exomes) in Japanese lung adenocarcinomas. We chose consecutive 97 of surgically resected T2 cases registered to the database containing clinicopathological and lifestyle information established at National Cancer Center Hospital East. High integrity genomic DNA was extracted from archived methanol fixed paraffin embedded tissue samples. Whole exons were captured using Agilent SureSelect system and we generated 76-base paired-end sequences with an Illumina GAIIx platform. Approximately 30 million mapped sequences were obtained for each sample, providing 75x coverage of the target regions and 93% of the target regions also had 5x coverage. Using the sequence data, we identified SNVs and indels by BWA, SAMtools and GATK. EGFR mutations were observed among 55 cases and Sanger sequencing validated them. As well, known lung cancer-related gene mutations such as KRAS and TP53 were detected in exome data. Detailed profiling of somatic mutations provided wide variety of heterogeneity of known and novel gene mutations with both EGFR-mutant and -wildtype background. These heterogenity might define the unique signature of an individual tumor and be waited for further classification suitable for understanding genetic mechanism of carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5134. doi:1538-7445.AM2012-5134