Differentiation imbalance in single oesophageal progenitor cells causes clonal immortalization and field change

摘要: Multiple cancers may arise from within a clonal region of preneoplastic epithelium, phenomenon termed 'field change'. However, it is not known how field change develops. Here we investigate this question using lineage tracing to track the behaviour scattered single oesophageal epithelial progenitor cells expressing mutation that inhibits Notch signalling pathway. frequently subject inactivating in squamous cancers. Quantitative analysis reveals cell divisions produce two differentiated daughters are absent mutant progenitors. As result, clones no longer lost by differentiation and become functionally immortal. Furthermore, promote neighbouring wild-type cells, which then tissue. These effects lead expansion, with eventually replacing entire epithelium. inhibition progenitors carrying p53 stabilizing mutations creates large confluent regions doubly Field thus consequence imbalanced individual cells.