Chromosomal translocations leading to activation of proto-oncogenes

In some cancerous cells; chromosomal translocations have been  discovered, where an oncogene of one chromosome is brought into the proximity  of an Ig locus on another chromosome (e.g. plasmacytomas in the mouse  and Burkitt lymphomas in man). Such translocations lead to activation of a  proto-oncogene like c-myc (Fig. 45.5), which is located on chromosome 8  in humans and on chromosome 15 in mouse. Due to translocation, the c-myc is  brought in close proximity of Ig gene on chromosome 14 in humans and  chromosome 12 in mouse.
Another case, where a translocation activates an  oncogene involves Philadelphia (PH1) chromosome found in chronic  myelogenoup leukemia (CML). This translocation involves transfer of a 5000kb  region from the end of chromosome 9 carrying c-abl to the bcr locus  (breakpoint cluster region = 5.8kb) of chromosome 22 (Fig. 45.6). This  translocation gives a bcr-abl fusion protein of 210,000 daltons (70,000 belonging  to bcr and ~ 140,000 is c-Abl protein). Perhaps the fusion, or loss of  N-terminal sequence, changes the conformation of c-Abl protein and activates a  latent oncogenic potential.

Translocations leading to activation of c-myc gene; in B cells c-myc is translocated to the proximity of Ig locus, while in T cells, it is translocated to the vicinity of TcRα locus (in both cases c-myc gets activated).
Fig. 45.5.  Translocations leading to activation of c-myc gene; in B cells c-myc is  translocated to the proximity of Ig locus, while in  T cells, it is translocated to the vicinity of TcRα locus (in both cases c-myc gets activated).
A translocation between chromosome 22 and chromosome 9 generating a Philadelphia chromosome (PH1), associated with chronic myelogenous leukemia (CML).
Fig. 45.6. A  translocation between chromosome 22 and chromosome  9 generating a Philadelphia chromosome (PH1), associated with chronic myelogenous leukemia (CML).
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