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

A. Rashid, J. S. Wang, G. S. Qian, B. X. Lu, S. R. Hamilton, J. D. Groopman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-66
Number of pages8
JournalBritish journal of cancer
Volume80
Issue number1-2
DOIs
StatePublished - 1999

Keywords

  • Aflatoxin
  • Hepatitis B virus
  • Hepatocellular carcinomas
  • Loss of heterozygosity
  • p53 gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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