Utilizing DNA mutations to trace epithelial cell lineages in human tissues.
Epithelial stem cells are typically multipotential and are likely the cell of origin of epithelial cancers. Tracing the expansion of a single stem cell's progeny, identifying and characterizing these cells in human tissue has proven difficult. Invasive labeling studies, which have led to much success in model organisms, are impracticable in humans. Instead, human studies must rely upon naturally occurring clonal markers: typically somatic DNA alterations that uniquely identify a population of cells with the same ancestry. In normal epithelium, nonpathogenic mitochondrial DNA mutations have proven useful. In premalignant and malignant disease, genomic DNA mutations within tumor suppressor genes or oncogenes can be used to trace the spread of mutant clones.
Centre for Digestive Diseases, Blizard Institute for Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
Sebastian
S
Zeki
Trevor A
TA
Graham
Stuart A C
SA
McDonald
D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology
D004272:DNA, Mitochondrial; D005819:Genetic Markers