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

• Published in: Cancer research (Chicago, Ill.) Vol. 58; no. 23; pp. 5333 - 5336
• Main Authors: SLEBOS, R. J. C, RESNICK, M. A, TAYLOR, J. A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-12-1998
• Subjects: Alu Elements; Base Sequence; Biological and medical sciences; DNA Transposable Elements; DNA, Neoplasm - genetics; Exons; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Gene Rearrangement; Genes, p53; Humans; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Molecular Sequence Data; Pancreatic Neoplasms - genetics; Tumor Cells, Cultured; Tumors; Human; Malignant tumor; Inactivation; In vitro; Alu sequence; TP53 Gene; Insertion mutation; Established cell line; Gene rearrangement; Deletion; Digestive diseases; Genetics; Pancreas; Tumor cell; Pancreatic disease; Tumor suppressor gene
• ISSN: 0008-5472; 1538-7445

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.