P53 mutation in phenacetin-induced urothelial carcinomas
Petersen, I.; Ohgaki, H.; Ludeke, B.I.; Kleihues, P.
Verhandlungen der Deutschen Gesellschaft für Pathologie 77: 252-255
1993
ISSN/ISBN: 0070-4113 PMID: 7511292 Document Number: 409110
We investigated 16 urothelial carcinomas from 13 patients with evidence of phenacetin abuse for p53 mutations by single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing. p53 mutations were detected in 8 of 14 primary tumors (57%). Missense mutations were located in exon 5 (3 mutations), exon 6 (1), exon 7 (2) and exon 8 (1). An insertion of a single cytosine in exon 5 was detected in a bladder tumor and its lung metastasis. In one patient, urothelial carcinomas in the renal pelvis and in the ureter exhibited two different mutations, strongly suggesting that these tumors developed independently. In contrast, the tumors in the renal pelvis and bladder of another patient contained the same mutation, indicating intracavitary metastatic spread. Our data support the view that phenacetin causes urothelial carcinomas through chronic tissue damage rather than promutagenic DNA lesions.