Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets

There has been considerable debate about the origin of human tumours, whether they arise from a single cell and are clonal populations or whether there needs to be some sort of co-operativity between cells for the neoplastic process to begin. Current theories subscribe to the clonal view, where a series of mutations in one cell begins a process of selection and clonal evolution leading to the development of the malignant phenotype. This review approaches this problem by asking how mutated clones, once established, spread through tissues before becoming overtly invasive. While there is substantial evidence in favour of independent origins of each tumour from a unique mutated clone, there are instances where such clones expand and remain cohesive, often involving a large area of tissue. The main example is the movement of mutated clonal crypts through the colorectal epithelium, by the process of crypt fission. In passing, the clonal architecture of early, pre-invasive lesions is examined, often with some surprising results.