[p53 mutation in phenacetin-induced urothelial carcinomas].
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.
Petersen
I
I
Institut für Neuropathologie, Departement Pathologie, Zürich.
Ohgaki
H
H
Ludeke
B I
BI
Kleihues
P
P
D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010615:Phenacetin / Q000009:adverse effects*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D019966:Substance-Related Disorders; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014516:Ureteral Neoplasms / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics; D014571:Urologic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology
D016159:Tumor Suppressor Protein p53; D010615:Phenacetin