The mechanisms responsible for creating genetic errors and
genomic instability in
cancer cells have not been fully defined. Recently, it has been shown that human cells contain a highly organized complex of
proteins, termed the
DNA synthesome, that is fully competent to carry out all phases of SV40 in vitro DNA replication (J. M. Coll et al, Oncol. Res., 8: 435-447, 1996; L. H. Malkas et al., Biochemistry, 29: 6362-6374, 1990; Y. Wu et al., J. Cell. Biochem., 54: 32-46, 1994; N. Applegren et al., J. Cell. Biochem., 54: 32-46, 1994). DNA replication fidelity analyses of the
DNA synthesome derived from malignant and nonmalignant human breast cells demonstrate that the malignant cell synthesome is mutagenic. The decrease in
tumor cell replication fidelity was not due to an increased proliferative capacity of the
tumor cells or an increase in the synthetic activity of their
DNA synthesome. The ratios of insertions, deletions, and mismatches created by the synthesome from malignant and nonmalignant breast cells were essentially identical, despite the greater overall number of mutations made by the
breast cancer cell synthesome. These data define, for the first time, a mechanism unique to
cancer cells that contributes to the observed increase in genetic mutation in
cancer cells.