Multistage carcinogenesis in Barrett's esophagus.
The multistage carcinogenesis of esophageal adenocarcinoma is a process of clonal evolution within Barrett's esophagus neoplasms. The initiating event for Barrett's esophagus is unknown, but is associated with chronic gastric reflux which probably also promotes progression. Inactivation of both alleles of CDKN2A appear to be early events causing clonal expansion. Clones with TP53 inactivated expand if they have already inactivated CDKN2A. After TP53 has been inactivated, tetraploid and aneuploid clones tend to develop. The final events that lead to invasion and metastasis are unknown. Evolutionary biology provides important tools to understand clonal evolution in progression and cancer prevention.
Maley
Carlo C
CC
The Wistar Institute, Cellular and Molecular Oncogenesis, 3601 Spruce Street, Philadelphia, PA 19104, USA. cmaley@alum.mit.edu
D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology*; D002908:Chronic Disease; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D005764:Gastroesophageal Reflux / Q000150:complications; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53