Inactivation of the p53 tumor suppressor gene via a novel Alu rearrangement.

Slebos RJ, Resnick MA, Taylor JA
Cancer Res. 1998 58 (23): 5333-6

PMID: 9850060

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.

MeSH Terms (12)

Alu Elements Base Sequence DNA, Neoplasm DNA Transposable Elements Exons Gene Expression Regulation, Neoplastic Gene Rearrangement Genes, p53 Humans Molecular Sequence Data Pancreatic Neoplasms Tumor Cells, Cultured

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