Genetic mutations in lung enteric adenocarcinoma identified using next-generation sequencing

Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphological and immunohistochemical characteristics are similar to those of metastatic colorectal carcinoma, but there is no associated primary colorectal carcinoma. The purpose of this study is to identify mutations by assessing the genetic profile of lung enteric adenocarcinoma with next-generation sequencing (NGS). This study included 11 lung enteric adenocarcinoma patients (5 males and 6 females) from three different centers who received treatment between Feb 2013 and Dec 2016. Immunohistochemical analysis failed to reveal any markers that differentiated this carcinoma from primary gastrointestinal adenocarcinoma. NGS analysis identified ALK/ROS1 primary point mutations in 5 patients (71.42%, 5/7) and MSH2/MSH6 point mutations in 3 patients (42.86%, 3/7). There was no case with drive genes changed, such as EGFR mutation, ALK rearrangement, ROS1 rearrangement, RET rearrangement, MET amplification or 14 exon skipping mutation. The median overall survival of the 11 lung enteric adenocarcinoma patients was 9.0 months. Further, subgroup analysis showed that the median OS of patients with ALK/ROS1 primary point mutations was 6.5 months and that of patients with MSH2/MSH6 primary point mutations was 26.0 months. These two mutations were the most frequent features, but this carcinoma generally showed genetic heterogeneity. Even though we have revealed some hitherto unidentified genetic mutations associated with lung enteric adenocarcinoma, the findings are preliminary and further investigations on more patients will be required to validate our findings.