Abstract
Anaplastic lymphoma kinase (ALK) fusion occurs in 3-5% of NSCLC, often in younger patients, with a slight predominance of women, light smokers, or non-smokers with adenocarcinoma. The ALK gene is most often fused to the EML4 (echinoderm microtubule associated protein-like 4) gene.
EML4 is located on the p21 protein of human chromosome 2, while ALK is located on the p23 protein. These two genes then form a new EML4-ALK gene via inverse fusion (Figure 1).
The EML4-ALK fusion has more than 21 different forms depending on the breakpoint. The sensitivity of different fusion forms to ALK inhibitors may vary.
ALK fusion proteins promote tumor growth and survival through aberrant activation of signaling pathways involved in the regulation of cell survival and proliferation.