Infrequent alterations of the p16(INK4A) gene in liver cancer

We examined the genomic status of the p16(INK4A) (inhibitor of cyclin-dependent kinase 4 A) and cyclin dependent kinase 4 (CDK4) genes in 62 human hepatocellular carcinomas (HCCs), 5 cholangiocellular carcinomas and 6 cell lines derived from human liver cancers, Although no samples showed the homozygous deletion of the p16(INK4A) gene, we detected intragenic mutations of the p16(INK4A) gene in 3 HCCs and one HCC cell line, which led to an amino-acid substitution or a frameshift. In 2 HCC samples with mis-sense mutations of the p16(INK4A) gene, loss of heterozygosity on 9p22 was also detected, suggesting that the loss of function of p16 was induced during hepatocarcinoegenesis. On the other hand, amplification or rearrangement of the CDK4 gene was not detected in any samples examined in this study. These results indicated that the mutations or deletions of the p16(INK4A) gene are not frequent, but may play a role in a sob-set of human HCC. (C) 1996 Wiley-Liss, Inc.