title: Polymorphisms and mutations found in the regions flanking exons 5 to 8 of the TP53 gene in a population at high risk for esophageal cancer in South Africa.
abstract: A previous study in esophageal cancer (EC) patients from South Africa showed that 17% of tumors contained somatic mutations, including small deletions, insertions, and point mutations, resulting in frameshifts or amino acid changes in exons 5-8 of the TP53 gene. In the present study, polymerase chain reaction single-strand conformation polymorphism and DNA sequence analysis were used to search for sequence variation in the regions flanking exons 5-8 in a series of 74 primary human esophageal squamous cell carcinomas (ESCC). DNA from blood from 37 of the same EC patients and 118 blood samples from the same ethnic group, originating from the Transkei region of South Africa, a high-risk area for EC, served as controls. Mutations were rarely found in the regions flanking exons 5-8, but polymorphisms were frequent. Two mutations (G-->A, codon 331; G-->T, donor splice site) were found in the exon 9 region, while four polymorphisms occurred in intron 3 (16 bp duplication) and exon 4 (C-->A, codon 34; G-->C, codon 36; G-->C, codon 72) regions. Loss of heterozygosity occurred for the 16 bp polymorphism in the EC patients, but not in the controls. Certain genotypes were common in the EC group while others were common in the control group. Graphic representation illustrates the various mutations/polymorphisms found in the TP53 gene in samples from EC patients from South Africa. The results indicate that various small deletions and insertions occur at direct repeat sequences and can be explained by slipped mispairing. The point mutations include the polymorphism in codon 72 (Arg-->Pro), which has recently been associated with an increased risk of developing human papilloma virus-associated cancers.
authors.affiliation: University of Stellenbosch, MRC Center for Molecular and Cellular Biology, Department of Medical Biochemistry, P.O. Box 19063, 7505, Tygerberg, South Africa.
authors.forename: Marelette
authors.initials: M
authors.lastname: Vos
authors.forename: Craig H
authors.initials: CH
authors.lastname: Adams
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Victor
authors.forename: Paul D
authors.initials: PD
authors.lastname: van Helden
mesh_terms: D044383:Black People / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics*; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005091:Exons / Q000235:genetics; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns / Q000235:genetics; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D013019:South Africa / Q000453:epidemiology
chemical_list: D003062:Codon; D004273:DNA, Neoplasm