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

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 76 BM 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.