MULTIPLE, UNIQUE, AND COMMON P53 MUTATIONS IN A THOROTRAST RECIPIENT WITH 4 PRIMARY CANCERS

Four primary cancers found at autopsy of a patient who received the th orium-based contrast agent Thorotrast 50 years ago and who was healthy up until a few months before his death from liver failure were analyz ed for p53 mutations. The data suggest that the chronic ct-irradiation may be a large causative factor. Multiple mutations were found in all the cancer tissues: two foci of a cholangiocellular carcinoma, a tubu lar adenocarcinoma of the stomach, a squamous cell carcinoma of the lu ng, and an adenocarcinoma of Vater's ampulla. The total number of poin t mutations detected were 13. Moreover, homozygous aberrations were de tected in a large area of normal small intestine and noncancer liver t issues suggesting that nontumor cells which harbored p53 abnormalities gained a survival advantage and clonally expanded. Copyright (C) 1998 by W.B. Saunders Company.