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Figure 9. Fluorescence in situ hybridization (FISH) of the malignant cells revealed involvement of the ALK1 gene on the short arm of chromosome 2. The green- and red-labeled probes anneal to opposite ends of the ALK1 gene such that intact ALK1 causes probe overlap and a resulting yellow signal, whereas chromosome breakage and subsequent translocation yields separate red and green signals. Note that one ALK1 gene remains intact (yellow), whereas the other ALK1 gene has been broken and translocated (separate red and green). Due to the nature of the probe used, the recipient locus of the translocated ALK1 could not be identified. A limited number of chromosomal translocations have been identified in ALCL, each involving ALK1. The most common translocation is t(2;5)(p23;q35), in which the N-terminus of the nuclear protein nucleophosmin (NPM) is fused to the C-terminus of ALK1, resulting in aberrant ALK1 nuclear localization. NPM-mediated heterodimerization between wild-type NPM and the NPM-ALK1 fusion is proposed to lead to nuclear localization due to the nuclear localization signal provided by NPM, whereas NPM-ALK1 homodimerization presumably activates ALK1, resulting in oncogenesis. Other translocations have also been identified, such as t(1;2)(q25;p23), which results in fusion of ALK1 with non-muscle tropomyosin, which localizes to the plasma membrane and cytoplasm. Similarly, other rare ALK1 translocations also tend to lead to cytoplasmic ALK1 localization.
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80% average survival rates compared to 
