Rearrangement of the receptor tyrosine kinase proto-oncogene ROS1, together with epidermal growth factor receptor (EGFR) gene mutations and the ALK gene rearrangements, “are the genetic alterations specific for lung cancer in never-smokers” and “compromise a unique and non-overlapping molecular subset,” according to new research published in Annals of Oncology.

Investigators evaluated tumor samples from 208 Korean adults with histologically confirmed lung adenocarcinoma; all participants reported smoking fewer than 100 cigarettes in their lifetime. Tumors were screened for ROS1 rearrangement using fluorescent in situ hybridization and confirmed by immunohistochemistry; tumors were also screened for ALK rearrangement and EGFR and KRAS mutations.

ROS1 rearrangement was detected in seven of 208 samples, giving a frequency of 3.4%. No tumor with ROS1 rearrangement had either ALK rearrangement or KRAS mutation; however, one ROS1-rearranged tumor had a concurrent EGFR mutation. CD74-ROS1 fusions were found in two ROS1-positive patients, while no fusion partner was found in the other five.

“This suggests that ROS1 rearrangement is a strong predictive factor for a longer median PFS to pemetrexed,” the authors wrote.”Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.”