MOLECULAR ANALYSIS OF THE TP53 GENE IN BARRETTS ADENOCARCINOMA

The TP53 gene is the most frequently mutated gene in human cancers. Ba rrett's esophagus provides an excellent model by which to understand t he genetic events that lead from dysplasia to cancer. We screened for mutations in the TP53 gene by a combination of denaturing gradient gel electrophoresis and DNA sequencing in ten cases of adenocarcinoma ari sing in Barrett's mucosa. We have identified missense mutations in fiv e of the ten samples, three transitions (R282W, G245S, R248W) and two transversions (B286Q and C176F). In one case we have analyzed biopsy s pecimens taken from the same site, one year before the patient develop ed an intra mucosal carcinoma. The mutation that was identified in thi s high grade dysplastic area was identical to that detected in the can cer. This would suggest TP53 mutations occur as an early genetic event in the development of Barrett's adenocarcinoma. (C) 1996 Wiley-Liss, Inc.