Base transitions at CpG dinucleotides in the p53 gene are common in esophageal adenocarcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 55; no. 15; pp. 3406 - 3411
• Main Authors: GLEESON, C. M, SLOAN, J. M, MCGUIGAN, J. A, RITCHIE, A. J, RUSSELL, S. E. H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.1995
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - pathology; Barrett Esophagus - genetics; Barrett Esophagus - pathology; Base Sequence; Biological and medical sciences; Chromosomes, Human, Pair 17 - genetics; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophagus; Exons - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Gene Deletion; Genes, p53; Humans; Medical sciences; Molecular Sequence Data; Nucleotides - genetics; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Sequence Analysis, DNA; Tumors; Chromosomal aberration; Adenocarcinoma; Human; Premalignant lesion; Pathogenesis; Esophageal disease; Barrett esophagus; Malignant tumor; Carcinogenesis; Esophagus; Tissue; Digestive diseases; Abnormal chromosome; Mutation; Abnormal E17 chromosome; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445

This study examined the association between 17p allelic loss and p53 gene mutation in a series of 16 esophageal adenocarcinomas arising on a background of Barrett's esophagus. Two highly polymorphic dinucleotide repeat polymorphisms mapping to 17p13 were analyzed to assess the frequency of 17p allelic loss in these tumors. Mutations in the p53 gene were detected by direct DNA sequencing. Ninety-four % (15 of 16) of samples were informative at one or both polymorphic loci. Allelic loss at one or both loci was detected in 80% (12 of 15) of samples. Mutations were detected in 69% (11 of 16) esophageal adenocarcinomas, and there was a close association between 17p allelic loss and p53 gene mutation (P = 0.00879; Fisher's Exact Test). The tumors that were analyzed demonstrated a specific p53 mutation spectrum, with G:C to A:T base transitions at CpG dinucleotides accounting for 80% (8 of 10) of single-base substitutions. In three cases, the same p53 mutation was detected in both high-grade dysplasia and adjacent tumor. These results indicate that p53 gene alterations contribute to the development of esophageal adenocarcinoma and precede the development of invasive carcinoma in patients with Barrett's esophagus.