Illustration depicting mutations attributable to environmental factors (right), DNA replication (center), and heredity (left)SCIENCE, C. TOMASETTI ET AL.Two years ago, researchers at Johns Hopkins University School of Medicine analyzed data on 31 cancer types, finding that the number of stem cell divisions within a tissue—over a lifetime—could partly explain the variation in cancer risk across different tissue types. In other words, the higher incidence of colon cancer versus brain cancer could be due to the relatively higher number of stem cell divisions in the colon compared to the relative infrequency of these divisions in the brain.
That study, by mathematician Cristian Tomasetti and cancer geneticist Bert Vogelstein of Johns Hopkins, sparked controversy in part because the results of the team’s analysis were misrepresented in some media reports, which declared that the study had indicated the proportion of cancers that arise from random DNA replication errors.
Now, extending and expanding upon their previous analysis, Tomasetti, Vogelstein, and biostatistics graduate student Lu Li—also at Johns Hopkins—have modeled the proportion of mutations in cancers that are due to the DNA replication errors that occur during normal stem cell divisions over the lifetime of a tissue. Based on their latest results, published today (March 23) in Science, the researchers have concluded that DNA replication error mutations are major contributors to the origins of cancers.
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