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, wheth er they arise from a single cell and are clonal populations or whether ther e 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 se ries of mutations in one cell begins a process of selection and clonal evol ution leading to the development of the malignant phenotype, This review ap proaches this problem by asking how mutated clones, once established, sprea d through tissues before becoming overtly invasive. While there is substant ial evidence in favour of independent origins of each tumour from a unique mutated clone, there are instances where such clones expand and remain cohe sive, often involving a large area of tissue. The main example is the movem ent of mutated clonal crypts through the colorectal epithelium, by the proc ess of crypt fission. In passing, the clonal architecture of early, pre-inv asive lesions is examined, often with some surprising results. Copyright (C ) 1999 John Wiley & Sons, Ltd.