Multiple, unique, and common p53 mutations in a thorotrast recipient with four primary cancers.
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.
Iwamoto
K S
KS
Department of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.
Mizuno
T
T
Kurata
A
A
Masuzawa
M
M
Mori
T
T
Seyama
T
T
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D000483:Alleles; D014670:Ampulla of Vater / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D018281:Cholangiocarcinoma / Q000235:genetics / Q000473:pathology; D003138:Common Bile Duct Neoplasms / Q000235:genetics / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D017809:Fatal Outcome; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D009378:Neoplasms, Multiple Primary / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology; D013911:Thorium Dioxide / Q000009:adverse effects*
D004273:DNA, Neoplasm; D013911:Thorium Dioxide