Multiple, unique, and common p53 mutations in a thorotrast recipient with four primary cancers

Hum Pathol. 1998 Apr;29(4):412-6. doi: 10.1016/s0046-8177(98)90126-5.


Four primary cancers found at autopsy of a patient who received the thorium-based contrast agent Thorotrast 50 years ago and who was healthy up until a few months before his death from liver failure were analyzed for p53 mutations. The data suggest that the chronic alpha-irradiation may be a large causative factor. Multiple mutations were found in all the cancer tissues: two foci of a cholangiocellular carcinoma, a tubular adenocarcinoma of the stomach, a squamous cell carcinoma of the lung, and an adenocarcinoma of Vater's ampulla. The total number of point mutations detected were 13. Moreover, homozygous aberrations were detected in a large area of normal small intestine and noncancer liver tissues suggesting that nontumor cells which harbored p53 abnormalities gained a survival advantage and clonally expanded.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Aged
  • Alleles
  • Ampulla of Vater / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / pathology
  • Common Bile Duct Neoplasms / genetics
  • Common Bile Duct Neoplasms / pathology
  • DNA, Neoplasm / analysis
  • Fatal Outcome
  • Genes, p53 / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Neoplasms, Multiple Primary / chemically induced
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Thorium Dioxide / adverse effects*


  • DNA, Neoplasm
  • Thorium Dioxide