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Scientists find normal rate of mutations in colon cancer cells


Colon cancer cells do not have more 'spontaneous' mutations than normal cells, according to a new study. Scientists found similar rates of DNA mutations in the genomes of normal cells and tumor cells isolated from the same patients. The findings suggest that cells with a normal number of mutations can develop into tumors.

Detail from schematic of mutation-discovery strategy. View larger

Although some cancers are inherited and therefore 'genetic,' many cancers seem to occur sporadically—that is, genetic mutations arise in cells during the course of a person's life. It has been unclear whether a higher frequency of mutations plays a role in cancers that occur sporadically.

To determine whether tumor DNA is characterized by more mutations, Victor E. Velculescu, of the Johns Hopkins Medical Institutions in Baltimore, and colleagues calculated the frequency of mutations in hundreds of genes throughout the genome. They sequenced regions of 470 genes in normal cells and tumor cells from twelve patients. A comparison of the results revealed that both cell types had similar mutation rates.

The findings "do not disprove the argument that genetic instability is an inherent feature of tumorigenesis," the researchers write in Proceedings of the National Academy of Sciences. "Instead, they emphasize that, although a subtle instability at the nucleotide level does not play a role in most colorectal cancers, a different form of genetic instability generally occurs in these tumors."

The genetic instability in these tumors probably occurred at the chromosomal level rather than the nucleotide level, says Velculescu. His laboratory investigates how a cancer cell genome differs from that of a non-cancerous cell. The current study was done in collaboration with Bert Vogelstein's laboratory at Johns Hopkins.

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Wang, T.-L. et al. Prevalence of somatic alterations in the colorectal cancer cell genome. Proc Natl Acad Sci USA 99, 3076-3080 (March 5, 2002).

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