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Mutation, clonal fitness and field change in epithelial carcinogenesis
Author(s) -
Frede Julia,
Adams David J,
Jones Philip H
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4409
Subject(s) - biology , carcinogenesis , stem cell , crypt , clone (java method) , mutant , somatic evolution in cancer , cell lineage , lineage (genetic) , mutation , epithelium , genetics , cancer , cancer research , microbiology and biotechnology , cellular differentiation , gene , endocrinology
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. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.