In this instance the genetic inversion EML4-ALK, found in approximately 5% of NSCLC patients, was modeled in a lung SEMM where two sgRNAs targeted the intronic region of Eml4 and Alk. While in vitro the two double strand breaks resulted in a variety of combinations including indels, deletions and inversions, in vivo the fusion Eml4-Alk was positively selected and drove the formation of NSCL with histopathological feature overlapping with the human disease. Here, EML4 is linked to non-small cell lung carcinoma.