p53-mutant clones and field effects in Barrett's esophagus.
Previous studies have demonstrated multifocal neoplasia in Barrett's esophagus. We evaluated 213 mapped, flow-purified, endoscopic biopsies to determine the distribution of p53-mutant clones in the Barrett's segments of 58 patients who had high-grade dysplasia without cancer. Twenty-nine patients (50%) had p53 mutations in their Barrett's segments, including 3 patients with multiple distinct p53 mutations. p53-mutant clones, including diploid cell populations, underwent expansion from 1 to 9 cm in the Barrett's segment. In 12 of 29 patients (41%) with a p53 mutation, the same mutation was found at every evaluated level of the metaplastic epithelium. This extensive p53-mutant clonal expansion suggests a somatic genetic basis for previous observations of field effects in Barrett's esophagus.
Prevo
L J
LJ
Program in Cancer Biology, Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Sanchez
C A
CA
Galipeau
P C
PC
Reid
B J
BJ
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D019943:Amino Acid Substitution; D001471:Barrett Esophagus / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003001:Cloning, Molecular; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D016368:Frameshift Mutation; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics*
D016159:Tumor Suppressor Protein p53