Biomedical Engineering Reference
In-Depth Information
Figure 16.2
Signaling via ALK.
16.2.3
The ALK Gene Rearrangements in Cancer
Many receptor tyrosine kinases have been implicated in oncogenesis
due to genetic abnormalities that range from point mutations, gene
amplifications, and chromosomal translocations. Whatever the
mechanism, the activation of the kinase catalytic domain results
in the growth factor-independent proliferation and anti-apoptotic
signaling. The most common mechanism of constitutive ALK
activation results from chromosomal translocations or inversions
involving the 2p23 chromosomal locus where the ALK gene is
located. The fusion of various genes at the 5
′
end with the cytoplasmic
domain of ALK at the 3
end creates oncogenic ALK fusion genes.
Since the initial discovery of the NPM-ALK fusion protein in patients
′
