ALK EML4-ALK E20;A20

EML4-ALK变异体2包括ALK激酶域（外显子20-29）与EML4外显子1-20的融合。变体2具有胞质分布，在NSCLC中约占EML4-ALK融合的10%。尽管特异性变异体的报道并不一致，但单例NSCLC对环唑天宁治疗有反应，并有一种来源不明的分化恶性肿瘤的报道。在体外，该变异体对TAE684和环唑替尼抑制ALK的敏感性高于EML4-ALK变异体1（E13；A20）、3A（E6；A20）和3B（E6ins33；A20）。据报道，该变异体在细胞中的稳定性不如其他变异体，可能是hsp90的客户蛋白。沿着这些线，变异体显示了对hsp90抑制的临床前敏感性。
EML4-ALK variant 2 consists of a fusion of the ALK kinase domain (exons 20-29) with EML4 exons 1-20. Variant 2 has cytoplasmic distribution and makes up ~10% of EML4-ALK fusions found in NSCLC,. Although the specific variant is not consistently reported, single cases demonstrating response to crizotinib treatment in NSCLC and a differentiated malignant neoplasm of unknown origin have been reported. In vitro, this variant has shown greater sensitivity to ALK inhibition with TAE684 and crizotinib than the EML4-ALK variants 1 (E13;A20), 3a (E6;A20) and 3b (E6ins33;A20). The variant was reported to be less stable in cells than other variants, and may be a client protein of Hsp90. Along these lines the variant has shown preclinical sensitivity to Hsp90 inhibition.