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~ 61,300

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The number of polyps in FAP patients does not grow linearly with time. Instead, most polyps appear 'suddenly' in the second decade of life. These observations are consistent with the predictions of our model. It is believed that polyps result from dysplastic crypts by means of further somatic mutations and clonal expansions. Therefore, the number of polyps is expected to be a higher than linear power of time, which looks like a steep increase in the number of lesions after a relatively non-eventful period. Also, the number of dysplastic crypts (103 — 104 in our model) is expected to be much larger than the number of polyps (102 — 103) consistent with the expectation that not all dysplastic crypts progress to polyps.

Another prediction of this model is that the fraction of MSI crypts in patients with FAP is negligible. This is consistent with an experimental study where MSI was found in none of the 57 adenomas from FAP patients [Keller et al. (2001)].

Finally, we note that the logical possibility exists that the second copy of the APC gene in FAP patients may be inactivated by an epigenetic event, just like the second copy of an MSI gene can be silenced by methylation. Experimental investigations [Menigatti et al. (2001)] however suggest that this is unlikely: out of the 84 FAP tumors, only 1 exhibited hypermethyla-tion of the APC gene.

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