Relating evolutionary selection and mutant clonal dynamics in normal epithelia.

ABSTRACT: Cancer develops from mutated cells in normal tissues. Whether somatic mutations alter normal cell dynamics is key to understanding cancer risk and guiding interventions to reduce it. An analysis of the first incomplete moment of size distributions of clones carrying cancer-associated mutations in normal human eyelid skin gives a good fit with neutral drift, arguing mutations do not affect cell fate. However, this suggestion conflicts with genetic evidence in the same dataset that argues for strong positive selection of a subset of mutations. This implies cells carrying these mutations have a competitive advantage over normal cells, leading to large clonal expansions within the tissue. In the normal epithelium, clone growth is constrained by the limited size of the proliferating compartment

SUBMITTER: Hall MWJ 

PROVIDER: S-EPMC6685019 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature