Schematic representation of the EML-4 and ALK translocation. A) Fusion of the N-terminal portion of EML4 (comprising the basic region, the HELP domain and part of the WD-repeat region) to the intracellular region of ALK (including the tyrosine kinase domain). TM, transmembrane domain. B) Both the ALK gene and the EML4 gene plot to chromosome 2p, but have opposite orientations. In the NSCLC EML4 is interrupted at a position 3.6 kb downstream of exon 13 and is attached to a position 297 bp upstream of exon 21 of ALK, creating the EML4-ALK (variant 1) fusion gene.