Germ-line mutations of the p16INK4(MTS1) gene occur in a subset of patients with hepatocellular carcinoma

Hepatology. 1997 Jun;25(6):1376-81. doi: 10.1002/hep.510250613.


The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very recently has there been a suggestion of familial hepatocellular carcinoma (HCC). We have analyzed the status of the p16INK4(MTS1) gene, a cyclin-dependent kinase inhibitor, in 26 patients with HCC of different etiologies. Four patients carried hemizygous germ-line point mutations of the p16INK4(MTS1) gene, suggesting the existence of familial HCC involving this gene. The wild-type allele was lost in the tumor in 2 of these 4 patients. Three of the patients carrying a germ-line mutation had non-cirrhosis-associated HCC. No somatic mutations of p16INK4(MTS1) were observed in the 26 cases of HCC. The most common somatic alteration of the p16INK4(MTS1) gene in HCC was de novo methylation, which was detected in 48% of the cases. Low levels (21%) of p16INK4(MTS1) gene allele loss were observed. Altogether, these results indicate that alteration of the p16INK4(MTS1) gene plays an important role in the genesis of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Carcinoma, Hepatocellular / genetics*
  • Carrier Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Methylation
  • Exons
  • Female
  • Genes, Tumor Suppressor*
  • Germ-Line Mutation*
  • Humans
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Promoter Regions, Genetic
  • Proteins / genetics
  • Tumor Suppressor Protein p14ARF


  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Proteins
  • Tumor Suppressor Protein p14ARF