Mechanisms of oncogene activation

A cellular oncogene controls cell division. It
controls the time and location of the orderly
proliferation of cells and tissues (normal
growth). Genetic changes can lead to disorders
of the regulation of cell divison, increased proliferation
of cells, and formation of a tumor. This
can be traced back to relatively few mechanisms.
A point mutation in a critical region of
the gene can lead to disturbances in the regulation
of cell division. Examples are mutations in
codon 12 or 63 or the H-ras gene.
An inactive cellular oncogene may become activated
when it is moved by chromosomal translocation
to the vicinity of an active gene. In
Burkitt lymphoma, an inactive gene is moved to
the region of an active gene for the H or L chain
of an immunoglobulin. In other cases, the
breakpoint of the chromosome translocation
may lie within a cellular oncogene and thereby
affect its expression. An example is the
Philadelphia translocation (see p. 332). Multiplication
(amplification) of a gene is a futher
mechanism that can lead to altered (usually increased)
expression.