title: Inactivation of the p53 tumor suppressor gene via a novel Alu rearrangement.
abstract: Inactivation of the p53 tumor suppressor gene is a common finding in human cancer. In most cases, inactivation is due to a point mutation in the gene, but rearrangement of the p53 gene is sometimes observed. We analyzed the inactivation of p53 in the human pancreas cancer cell line Hs766T, which harbors a structural alteration in the p53 gene. This inactivation was found to be the result of a complex deletion/insertion event involving at least two different Alu elements. The rearrangement eliminated exons 2-4 from the p53 gene, whereas a 175-bp Alu fragment was inserted between the breakpoints of the deletion. DNA sequence analysis of this Alu fragment revealed that it is identical to an Alu element in intron 1 of the p53 gene. This is the first report of p53 inactivation due to a rearrangement involving Alu elements. This type of inactivation may go unnoticed when only traditional methods to detect p53 alterations are used.
authors.affiliation: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. slebos@niehs.nih.gov
authors.forename: R J
authors.initials: RJ
authors.lastname: Slebos
authors.forename: M A
authors.initials: MA
authors.lastname: Resnick
authors.forename: J A
authors.initials: JA
authors.lastname: Taylor
mesh_terms: D020087:Alu Elements; D001483:Base Sequence; D004251:DNA Transposable Elements; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004251:DNA Transposable Elements; D004273:DNA, Neoplasm