Genetic alterations in hepatocellular carcinomas: association between loss of chromosome 4q and p53 gene mutations

Br J Cancer. 1999 Apr;80(1-2):59-66. doi: 10.1038/sj.bjc.6690321.


The major risk factors for hepatocellular carcinomas (HCC) in high incidence areas include infection with hepatitis B and C viruses (HBV, HCV) and exposure to aflatoxin. Genetic alterations in 24 liver resection specimens from Shanghai and Qidong were studied. Hepatitis B virus was integrated in all patient samples, and a null phenotype for the GSTM1 enzyme was present in 63% of patients. Alteration of p53 was present in 95% (23/24) of cases: mutations of the p53 gene in 12 HCC, p53 overexpression in 13 and loss of heterozygosity (LOH) of chromosome 17p in 17. All seven HCCs with a p53 mutation from Qidong and three of five from Shanghai had the aflatoxin-associated point mutation with a G to T transversion at codon 249, position 3. No HCC had microsatellite instability. LOH of chromosome 4q, 1p, 16q and 13q was present in 50%, 46%, 42% and 38%, respectively, and 4q was preferentially lost in HCCs containing a p53 mutation: LOH of 4q was present in 75% (9/12) of HCC with, but only 25% (3/12) of HCC without, a p53 gene mutation (P = 0.01). These data indicate a possible interaction between p53 gene mutation and 4q loss in the pathogenesis of HCC.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • China
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 4 / genetics*
  • DNA / analysis
  • Epoxide Hydrolases / genetics
  • Genes, p53* / genetics
  • Glutathione Transferase / genetics
  • Hepatitis B / complications
  • Hepatitis B / diagnosis
  • Hepatitis B Antigens / isolation & purification
  • Hepatitis C Antigens / isolation & purification
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Loss of Heterozygosity*
  • Microsatellite Repeats
  • Mutation
  • Polymerase Chain Reaction


  • Hepatitis B Antigens
  • Hepatitis C Antigens
  • DNA
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Epoxide Hydrolases