This report describes a model of gastric cancer, TPM4-ALK fusion, which represents one of the more common translocations associated with gastric cancer. The two human genes involved in this translocation are ALK, which encodes a neuronal receptor tyrosine kinase that belongs to the insulin receptor superfamily, and TPM4, which encodes a member of the tropomyosin family of actin-binding proteins. The TPM4-ALK gene fusion results in constitutive activation of the ALK kinase domain.
The Drosophila model of this disease is based on the introduction of a UAS construct of the human fusion gene (indicated as Hsap\ALK::Hsap\TPM4) into flies; the phenotypes resulting from ubiquitous overexpression of this construct have been compared to constructs carrying Hsap\ALK alone or Hsap\TPM4 alone. Flies expressing any of the three show decreased lifespans compared with controls, with a more dramatic decrease observed for the fusion construct. Rescue of the reduced lifespan phenotype has been used to characterize effects of the therapeutic agent crizotinib.
See also the human disease model report 'cancer, multiple, ALK-related' (FBhh0000713).
[updated Jan 2020 by FlyBase; FBrf0222196]
TPM4 encodes a member of the tropomyosin family of actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. [Gene Cards, TPM4; 2020.01.16]
ALK encodes a neuronal receptor tyrosine kinase that belongs to the insulin receptor superfamily. [Gene Cards, ALK; 2020.01.16]
One to one: 1 human to 1 Drosophila.
Many to many: 4 human to 2 Drosophila; the other human genes are TPM1, TPM2, and TPM3.
