New Fusion Genes In Lung Adenocarcinoma Revealed From Next Generation Rna-Seq

Cancer is a genomic disease. A subset of somatic driver mutations has been reported in lung adenocarcinoma in the past few years, such as somatic mutations in EGFR, KRAS and EML4-ALK fusion gene. Identification of driver mutations in lung cancer is very important, since several anti-cancer drugs targeting them (gefitinib, erlotinib, and crizotinib) have shown dramatic clinical outcomes for the treatment of lung adenocarcinomas. However, a large proportion of lung cancer patients have been observed to have none of them in their cancer genome. More than 40% of lung adenocarcinoma patients appear to be driven by unknown genetic events. Gene fusions represent a subset of genetic alteration in human cancer. We recently identified a fusion gene joining KIF5B and RET transforming tyrosine kinase in tumor tissues of lung adenocarcinoma patients as a driver mutation using integration of whole-genome and transcriptome sequencing of cancer tissue [1]. We expanded our study by sequencing more transcriptomes of lung adenocarcinomas with paired normal tissues. Overall, we obtained transcriptome sequences from 88 primary lung adenocarcinomas, 53.5% (n=47) of them were negative for EGFR, KRAS and EML4-ALK. Our approach identified many novel fusion events in lung adenocarcinoma, such as CD74-ROS1, SLC34A2-ROS1, and additional fusions of cancer related genes. Majority of these fusion genes and known somatic mutations were mutually exclusive (p=0.001), suggesting these fusion genes are highly likely to be the driver mutations of lung adenocarcinoma. Overall, fusion genes account for ∼15% of genetic causes of lung adenocarcinoma according to our dataset. We will discuss those fusion genes and frequent somatic mutations of lung adenocarcinoma revealed from transcriptome sequencing of 88 lung adenocarcinomas. REFERENCE 1. Fusion of KIF5B and RET transforming gene in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Research (2012), Advance online publication Dec 22 2011. 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 LB-402. doi:1538-7445.AM2012-LB-402