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Inactivation of the p53 Tumor Suppressor Gene via a Novel Alu Rearrangement

Laboratory of Molecular Carcinogenesis [R. J. C. S., J. A. T.], Epidemiology Branch [J. A. T.], and Laboratory of Molecular Genetics [M. A. R.], National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

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.

¹ To whom requests for reprints should be addressed, at National Institute of Environmental Health Sciences, Laboratory of Molecular Carcinogenesis, Maildrop C2-01. P. O. Box 12233, Research Triangle Park, NC 27709. Phone: (919) 541-2694; Fax: (919) 541-2511; E-mail: slebos@niehs.nih.gov.

Received 9/ 8/98. Accepted 10/19/98.

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