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

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 i nactivation of p53 in the human pancreas cancer cell line Hs766T, which har bors a structural alteration in the p53 gene. This inactivation was found t o be the result of a complex deletion/insertion event involving at least tw o different Alu elements. The rearrangement eliminated exons 2-4 from the p 53 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 eleme nts. This type of inactivation may go unnoticed when only traditional metho ds to detect p53 alterations are used.