BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: Environmental factors are important in the etiology of hepatocellular carcinoma (HCC). Aflatoxin B1 causes a specific point mutation in the p53tumor-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 Britishpatients with HCC. The aim of this study was to determine the frequency and mutational spectrum of the p53 gene in HCCs from Britishpatients. METHODS: DNA from 170 HCCs, of well-defined etiology, in Britishpatients 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.
Authors: Andrea Hartwig; Michael Arand; Bernd Epe; Sabine Guth; Gunnar Jahnke; Alfonso Lampen; Hans-Jörg Martus; Bernhard Monien; Ivonne M C M Rietjens; Simone Schmitz-Spanke; Gerlinde Schriever-Schwemmer; Pablo Steinberg; Gerhard Eisenbrand Journal: Arch Toxicol Date: 2020-06-15 Impact factor: 5.153
Authors: S P Hussain; K Raja; P A Amstad; M Sawyer; L J Trudel; G N Wogan; L J Hofseth; P G Shields; T R Billiar; C Trautwein; T Hohler; P R Galle; D H Phillips; R Markin; A J Marrogi; C C Harris Journal: Proc Natl Acad Sci U S A Date: 2000-11-07 Impact factor: 11.205