Colorectal adenoma and cancer divergence. Evidence of multilineage progression.

摘要: Colorectal cancer progression involves changes in phenotype and genotype. Although usually illustrated as a linear process, more complex underlying pathways have not been excluded. The object of this paper is to apply modern quantitative principles molecular evolution multistep tumor progression. To reconstruct lineages, the genotypes two adjacent adenoma-cancer pairs were determined by serial dilution polymerase chain reaction at 28–30 microsatellite (MS) loci then traced back their most recent common ancestor. tumors mismatch repair deficient, therefore relatively large numbers MS mutations should accumulate during As expected, similar (correlation coefficients >0.9) between different parts same adenoma or cancer, but very <0.2) unrelated metachronous pairs. Unexpectedly, also 0.30 0.36), consistent with early divergence rather than direct More 60% divisions occurred after divergence. Therefore, phylogenies sequential stepwise selection along single “fit” frequent lineage from cancer. Instead, one effective strategy creates maintains multiple evolving candidate which are subsequently selected for terminal clonal expansion.