Vast majority of EML4-ALKÐpositive lung cancer is negative for active EGFR and active KRAS.

EML4 (echinoderm microtubule associated protein like 4)

2p21

981 amino acids; 109 kDa; microtubule associated protein.

ALK (anaplastic lymphoma receptor tyrosine kinase)

2p23.2

1620 amino acids; 176 kDa; membrane-associated tyrosine kinase receptor.

EML4-ALK(E2;A20) and EML4-ALK(E2;add117A20): Intron 2 of EML4 is ligated to intron 19 of ALK, generating an EML4-ALK mRNA where exon 2 of the former is fused to exon 20 of the latter (also referred to as variant 5a). From the same gene rearrangement, alternative splicing of messages further generates an mRNA where exon 2 of EML4 is connected to a position within intron 19 of ALK located 117 bp-upstream of exon 20 (also referred to as variant 5b).

All EML4-ALK fusion mRNAs encode proteins where a part of EML4 is fused to the cytoplasmic kinase domain of ALK. The amino-terminal coiled-coil domain within EML4 is necessary and sufficient for the transforming activity of EML4-ALK, probably through oligomerazing the fusion proteins.