Inactivation of the p53 gene, located on chromosome 17p, leads to genetic instability and aneuploidy in vitro. Aneuploid cell populations from Barrett's adenocarcinomas have a high prevalence of 17p allelic losses, and there is substantial evidence that the target of these losses is the p53 gene. If 17p allelic losses lead to aneuploidy in Barrett's esophagus, then they should be present in diploid cells from patients who develop aneuploidy. We detected 17p allelic losses in diploid cells from 10 of 11 patients (91%) with Barrett's esophagus who developed aneuploid cell populations. Our data strongly suggest that 17p allelic losses precede the development of aneuploidy during neoplastic progression in Barrett's esophagus in vivo and, therefore, support in vitro evidence for the role of p53 in genetic instability.
This research was supported by American Cancer Society Grants EDT-21E and EDT-37A, NIH Grant R01 CA55814, National Cancer Institute Grant K07 CA59555, the Ryan Hill Research Foundation, and the Office of Research and Development (Medical Research Service), Department of Veterans Affairs.