Spectrum of gene mutations detected by next generation exome sequencing in brain metastases of lung adenocarcinoma

Abstract Background Brain metastases (BM) are a life-threatening complication. We aimed to analyse gene mutations in lung adenocarcinoma BM. Methods We performed next generation sequencing (NGS) of a pre-defined set of 48 cancer-related genes in a cohort of 76 neurosurgical lung adenocarcinoma BM specimens using a cancer specific gene panel on the MiSeq platform (Illumina, San Diego, CA). NGS results were statistically correlated to patient characteristics. Data on ALK , ROS1 , MET and FGFR1 gene status assessed by FISH were available from previous studies in the majority of patients. Results Twenty-nine (60.4%) of the 48 investigated cancer-related genes were mutated in at least one BM sample and 64 (84.2%) of the 76BM samples carried at least one mutated gene. The number of mutated genes per sample ranged from 0 to 9 (median 2). The most commonly mutated genes were TP53 , KRAS and CDKN2A , which were affected in 35/76 (46.1%), 29/76 (38.2%) and 17/76 (22.4%) samples, respectively. Other potentially druggable alterations included EGFR mutations (3/76, 3.9% of samples), PIK3CA mutation (2/76, 2.6%), BRAF mutation (1/76, 1.3%) and SMO mutation (1/76, 1.3%). Presence of KRAS mutations was associated with positive smoking history ( p =0.015, Chi square test) and presence of EGFR mutation correlated with unfavourable overall survival time from BM diagnosis ( p =0.019, log rank test). Conclusions Deleterious gene mutations, some of them with potential therapeutic implications, are found in a high fraction of lung adenocarcinoma BM.