Gene amplification: an example of accelerated evolution in tumorigenic cells - PubMed (original) (raw)

Gene amplification: an example of accelerated evolution in tumorigenic cells

R Sager et al. Proc Natl Acad Sci U S A. 1985 Oct.

Abstract

During selection for methotrexate resistance, tumorigenic CHEF/16 cells and derivatives from CHEF/16 tumors underwent amplification of the dihydrofolate reductase gene (DHFR) at accelerated rates compared with closely related nontumorigenic CHEF/18 cells. "Dot blot" analysis showed that the CHEF/16 cells contained many more copies of the DHFR gene than did the CHEF/18 cells, when assayed at similar elevated levels of methotrexate resistance. Chromosome analysis of cell samples taken at several time points during amplification revealed large differences between the nontumorigenic CHEF/18 cells and the two tumorigenic cell lines. The tumorigenic cells developed few chromosome rearrangements over a 4-log increase in methotrexate resistance, other than increased length of a single chromosome, which was shown by in situ hybridization to contain most or all of the amplified DHFR gene copies. In contrast, the CHEF/18 cells underwent complex, progressive changes in almost every chromosome, and in situ hybridization suggested a dispersed pattern of gene amplification. The data support the hypothesis that unregulated amplification is a pathological process, occurring readily in neoplastic but rarely in normal cells, that together with other chromosomal disturbances contributes to the rapid evolution and progression of cancer.

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References

    1. Genetics. 1972 Oct;72(2):357-62 - PubMed
    1. Science. 1984 Nov 16;226(4676):792-801 - PubMed
    1. Mutat Res. 1976 Nov;40(4):325-37 - PubMed
    1. Hereditas. 1977;86(1):15-30 - PubMed
    1. Somatic Cell Genet. 1978 May;4(3):375-92 - PubMed

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