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Genetics, DNA & Disease

Genetic instabilities in human cancers.

It is widely accepted among researchers that cancer results from the accumulation of mutations in the genes that directly control the birth and death of cells, but the mechanisms remain unclear. The data reviewed in this article point to a conclusion that nearly all solid tumors are genetically unstable, and they frequently gain or lose entire chromosomes. In most cases, the instability is found at the chromosomal level, but in a few cases the instability is found at the nucleotide level and is caused by faulty DNA repair.

Chromosomal abnormalities are added to by translocations and amplifications, and these are thought to reflect additional mechanisms which generate instability in the tumor as it grows. Instability is responsible for both tumor growth and tumor heterogeneity, and guarantees that no two tumors are exactly alike. It also means that no tumor is composed of cells which are genetically identical. This heterogeneity of tumor cells, even within one tumor, make any particular therapeutic treatment difficult.

A lot of effort in research is going towards targeting the mutant oncogenes and tumor-suppressor genes that control tumor growth directly during treatment. It is believed that the instabilities in tumors are genetically based, and therefore permanent. Because these instabilities reflect defects in cellular processes in the tumor, it is expected that they will be sensitive to particular chemicals, and this may benefit the patient in allowing specific treatment directed at the mutant cells. Thus, although instability may be necessary for tumors to develop, it may also make them easier to destroy if their chemical sensitivities can be found.

The appearance of a human tumor culminates from a complex series of steps. The rate-limiting steps are thought to be caused by mutations in half a dozen or more cellular genes that directly or indirectly affect tumor cell p...

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