Frequent Mutation of the p53 Gene in Human Esophageal Cancer

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 24; pp. 9958 - 9961
• Main Authors: Hollstein, M. C., Metcalf, R. A., Welsh, J. A., Montesano, R., Harris, C. C.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1990; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; Alleles; Base Sequence; BASIC BIOLOGICAL SCIENCES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; Biological and medical sciences; BODY; BRAIN; Cancer; carcinoma; CARCINOMAS; Cell Line; Cell lines; CENTRAL NERVOUS SYSTEM; Codon - genetics; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; DISEASES; DNA; DNA SEQUENCING; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Esophageal Neoplasms - etiology; Esophageal Neoplasms - genetics; ESOPHAGUS; Exons; Fundamental and applied biological sciences. Psychology; GASTROINTESTINAL TRACT; GENE MUTATIONS; GENE REGULATION; GENES; Genes. Genome; Genetic loci; Genetic mutation; GLANDS; Humans; INTESTINES; ISOTOPES; LARGE INTESTINE; LIGHT NUCLEI; LUNGS; MAMMARY GLANDS; man; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; MUTATIONS; NEOPLASMS; NERVOUS SYSTEM; NUCLEI; ODD-ODD NUCLEI; Oligonucleotide Probes; ONCOGENES; ORGANS; p53 genes; p53 protein; PATHOGENESIS; PHOSPHORUS 32; PHOSPHORUS ISOTOPES; Polymerase Chain Reaction; RADIOISOTOPES; RESPIRATORY SYSTEM; squamous cells; STRUCTURAL CHEMICAL ANALYSIS; Tumor cell line; Tumor Cells, Cultured - metabolism; tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumors; Human; Cell line; Gel electrophoresis; Pathogenesis; Malignant transformation; Tumor; Mutation; Esophagus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.24.9958

Sequence alterations in the p53 gene have been detected in human tumors of the brain, breast, lung, and colon, and it has been proposed that p53 mutations spanning a major portion of the coding region inactivate the tumor suppressor function of this gene. To our knowledge, neither transforming mutations in oncogenes nor mutations in tumor suppressor genes have been reported in human esophageal tumors. We examined four human esophageal carcinoma cell lines and 14 human esophageal squamous cell carinomas by polymerase chain reaction amplification and direct sequencing for the presence of p53 mutations in exons 5, 6, 7, 8, and 9. Two cell lines and five of the tumor specimens contained a mutated allele (one frameshift and six missense mutations). All missense mutations detected occurred at G·C base pairs in codons at or adjacent to mutations previously reported in other cancers. The identification of aberrant p53 gene alleles in one-third of the tumors we tested suggests that mutations at this locus are common genetic events in the pathogenesis of squamous cell carcinomas of the esophagus.