The dynamics of early intestinal tumour proliferation: to be or not to be.

New data and approaches bring novel perspectives and possibilities to old problems. The speculation of this chapter attempts to merge the puzzling MS data observed in human tumours (Figs. 3 and 4B) within a multistep tumour progression model. Clearly the current models are gross simplifications and other, more sophisticated models may better account for the distribution of MS alleles found in human tumours. The findings and the data are also limited to MMR deficient tumours, and studies in non-mutator phenotype tumours may be more difficult since fewer polymorphisms will arise during progression. The current model, however, precisely defines proliferation and clearly delineates two very distinct patterns. Further studies using MS loci in MMR deficient tumours will allow fairer tests of alternative pathways (Fig. 4C) to cancer. Evolution proceeding in occult progenitor populations allows mutations to accumulate throughout life and not just in the last decades after polyps appear.