**2.1 Gene mutations**

Recent advances in next-generation sequencing (NGS) and other highthroughput genomic profiling platforms have allowed the examination of the breadth of genetic mutations within lung cancer. The most common mutation is in the Kirsten rat sarcoma (KRAS) oncogene, occurring in approximately 30% of adenocarcinomas (Ade) predominantly in patients with a history of smoking [5]. BRAF is mutated in approximately 3% of patients (with half of cases being the V660E mutation) [6]. Along with KRAS and BRAF, epidermal growth factor receptor (EGFR) mutations were discovered in patients with Ade and small cell lung cancer (SCLC) [5]. Moreover, mutations and amplifications in many oncogenes have been identified, including HER2, MET, as well as fusion oncogenes involving anaplastic lymphoma kinase (ALK), neuregulin 1 (NRG1), neurotrophic tyrosine kinase receptor type 1 (NTRK1), and RET [7–13]. Microtubule-associated protein-like 4 (EML4) and ALK fusion gene is another important driver gene in lung cancer, which was discovered by Soda et al. in 2007 [10]. In NSCLC, EML4/ ALK is an aberrant fusion gene that encodes a cytoplasmic chimeric protein with constitutive kinase activity. The incidence of EML4/ALK fusion in cohorts of patients with NSLCL ranges from 1.6% to as high as 19.3%. Genes such as discoidin domain-containing receptor 2 (DDR2); fibroblast growth factor receptor 1, 2, and 3 (FGFR1, FGFR2, FGFR3); and genes in the phosphatidylinositol 3 kinase (PI3K) pathway seem instead to be more commonly mutated in squamous cell carcinoma (SCC). Many of these mutations have been validated by preclinical studies as driver mutations [14–16]. Aberration in stem cell factor receptor tyrosine kinase (c-KIT), PI3K catalytic subunit alpha (PIK3CA), PI3K/AKT/mTOR, phosphatase and tensin homolog (PTEN), insulin-like growth factor receptor (IGFR1), and hedgehog (Shh) signaling pathways have been identified in lung cancer [7] (**Table 1**).
