Barrett's Esophagus: A Model of Human Neoplastic Progression

In 1976, Nowell hypothesized that cancer develops as a consequence of an acquired genomic instability that predisposes to the development of abnormal clones of cells with accumulated genetic errors (Nowell 1976). Some clones gain selective proliferative advantages, and eventually a subclone evolves that has acquired the capacity for invasion, becoming an early carcinoma. There is now substantial evidence that human cancers develop in association with a process of clonal evolution that leads to the accumulation of genetic errors (Vogelstein et al. 1988; Huang et al. 1992; Raskind et al. 1992; Sidransky et al. 1992). Many studies have investigated genetic abnormalities in advanced carcinomas in surgical specimens. Although the study of advanced cancers is useful for identifying genetic abnormalities that have accumulated in the cancer, this approach is limited in its ability to determine the order in which genetic and other abnormalities develop during earlier stages of neoplastic progression.