Tomasetti–Vogelstein model
The Tomasetti–Vogelstein model explains differences in cancer risk between tissues by the lifetime number of stem-cell divisions each tissue undergoes: the more replications a tissue’s stem cells perform, the more opportunities random replication errors have to produce a driver mutation.
The correlation
Tomasetti and Vogelstein plotted lifetime cancer incidence for 31 tissue types against the estimated cumulative number of stem-cell divisions in each, and found that the two correlate strongly (r = 0.81 in the 2015 “bad luck” paper). Cancers of the colon, with its constantly renewed epithelium, sit at the high-division end; bone and brain cancers sit at the low end. The 2017 follow-up classified cancer types by the fraction of driver mutations attributable to three sources: hereditary mutations, environmental exposures, and replication errors. Replication errors dominated in tissues with high division counts, and the authors estimated that about two-thirds of driver mutations across cancers arise this way.
What the model claims, and what it does not
The correlation is a claim about the supply of mutations, and it explains why tissues differ in baseline risk. It is compatible with the large environmental fraction of cancer: smoking, UV, and HPV raise mutation rates in the tissues they reach, and the model’s own 2017 analysis assigns those exposures their share. The public reading of the 2015 paper — that most cancer is “bad luck” and prevention is futile — was a misreading the authors explicitly corrected: prevention still works on the environmental share, and the replication-error share is exactly the component that early detection and fitness-landscape approaches address.
The model matters for this wiki because it quantifies the mutation supply side of somatic evolution: division count is the denominator that determines how often a tissue samples a driver, before selection decides what a driver is worth.
Notes
- Tomasetti C, Vogelstein B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015;347(6217):78–81.
- Tomasetti C, Li L, Vogelstein B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017;355(6331):1330–1334. 10.1126/science.aaf9011
- Critiques center on the stem-cell-division estimates and on the interpretation of the environmental fraction.