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. 1999 Oct;1(4):206-9.

Genetic instability in cancer: caretaker and gatekeeper genes

P Deininger  1
Affiliations

Genetic instability in cancer: caretaker and gatekeeper genes

P Deininger. Ochsner J. 1999 Oct.
No abstract available

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Figures

Figure 1.
Figure 1.
Typical mutations transforming a normal proto-oncogene into an oncogene. The most common types of mutations associated with oncogenes involve point mutations that alter the control of the oncoprotein made from the gene (as in the ras family of oncogenes), duplication of oncogenes resulting in higher expression of the oncogene, or chromosomal translocations that fuse the oncogene with a different gene. The latter change either results in an oncoprotein of altered function or results in changes in expression pattern of the oncogene
Figure 2.
Figure 2.
Simplified diagram of typical progression to colon cancer. The APC, DCC and p53 genes represent tumor suppressor genes that are often inactivated in this progression, resulting in poor growth control of the cells. K-ras represents one of several oncogenes that are commonly mutated in colon cancer progression, resulting in stimulation of tumor cell growth. Altered methylation of DNA results in changes in expression of genes associated with the methylation, and potentially contribute to some genomic instability. The msh2 and mlh1 genes are associated with DNA mismatch repair, and their mutation leads to rapid DNA mutation
Figure 3.
Figure 3.
Loss of a tumor suppressor. The tumor suppressor gene is represented as a black box on the short arms of the chromosomes. The first step in loss of the tumor suppressor gene is often deletion of all or part of one copy of the gene. Families with strong predispositions to cancer often have one copy of a tumor suppressor gene deleted. There are no direct negative effects of loss of only one copy of the tumor suppressor gene. However, eventually something occurs to silence the second copy of the tumor suppressor gene, through either mutation or methylation. At this point, the protein coded by the tumor suppressor gene is no longer available to help suppress cell growth
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