Tracing Cell Fates in Human Colorectal Tumors from Somatic Microsatellite Mutations

摘要: Occult aspects of tumor proliferation are likely recorded genetically as their microsatellite (MS) loci become polymorphic. However, MS mutations generated by division may also be eliminated with death noncoding lack selective value. Therefore, highly polymorphic cannot exist unless mutation rates high, or losses inherently minimized. Mutations accumulate differently when cell fates determined intrinsically before extrinsically after division. Stem (asymmetrical in intestinal crypts) and random symmetrical division) proliferation, respectively, represent simulated Whereas regardless selection systematically persist once inherited stem the both daughter cells proliferation. greater genetic diversity variance compared normal murine mucosa xenografts cancer lines accumulated mutations, consistent Tumors from patients hereditary nonpolyposis colorectal (HNPCC) demonstrated loci. Overall, three five adenomas one six cancers exhibited high variances. Assuming not significantly than cancers, these studies suggest hierarchy intestines persists many HNPCC some cancers. An adenoma architecture can explain complex observed account for features. In contrast, lose intrinsic control fate. These illustrate a feasible phylogenetic approach to unravel describe occult human The switch predominantly critical defining characteristic malignancy.