title: Mutation, clonal fitness and field change in epithelial carcinogenesis.
abstract: Developments in lineage tracing in mouse models have revealed how stem cells maintain normal squamous and glandular epithelia. Here we review recent quantitative studies tracing the fate of individual mutant stem cells which have uncovered how common oncogenic mutations alter cell behaviour, creating clones with a growth advantage that may persist long term. In the intestine this occurs by a mutant clone colonizing an entire crypt, whilst in the squamous oesophagus blocking differentiation creates clones that expand to colonize large areas of epithelium, a phenomenon known as field change. We consider the implications of these findings for early cancer evolution and the cancer stem cell hypothesis, and the prospects of targeted cancer prevention by purging mutant clones from normal-appearing epithelia.
authors.affiliation: MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge, CB2 0XZ, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Frede
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Philip H
authors.initials: PH
authors.lastname: Jones
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D004848:Epithelium / Q000473:pathology*; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*
keywords: cancer; epithelial carcinogenesis; field change