p53 mutations in british patients with hepatocellular carcinoma: clustering in genetic hemochromatosis.
OBJECTIVE
Environmental factors are important in the etiology of hepatocellular carcinoma (HCC). Aflatoxin B1 causes a specific point mutation in the p53 tumor-suppressor gene in exposed individuals. In Western populations, mutations of this gene seem to be less frequent. We have investigated the role of p53 mutations in tumorigenesis in British patients with HCC. The aim of this study was to determine the frequency and mutational spectrum of the p53 gene in HCCs from British patients.


METHODS
DNA from 170 HCCs, of well-defined etiology, in British patients was analyzed by single-stranded conformational polymorphism using the polymerase chain reaction technique. Mutations were then characterized by direct sequencing.


RESULTS
Twenty-nine percent of tumors had p53 mutations. Ten of 14 (71%) hemochromatotic cancers had mutations within the p53 gene, and clustering of these mutations at codon 220 (A-G) was found in 5 cases; 3 others had T-A mutations. No clustering was found in HCCs with other etiologies.


CONCLUSIONS
p53 mutations are more common than was thought in Northern European HCCs. This is the first demonstration of p53 mutational clustering in HCCs from hemochromatotic subjects.
Vautier
G
G
Department of Gastroenterology, University Hospital, Nottingham, England.
Bomford
A B
AB
Portmann
B C
BC
Metivier
E
E
Williams
R
R
Ryder
S D
SD
D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000150:complications / Q000235:genetics; D005787:Gene Frequency; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D005810:Multigene Family / Q000502:physiology; D009154:Mutation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D006113:United Kingdom
D016159:Tumor Suppressor Protein p53