title: Infrequent alterations of the p16INK4A gene in liver cancer.
abstract: We examined the genomic status of the p16INK4A (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 p16INK4A gene, we detected intragenic mutations of the p16INK4A 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 p16INK4A gene, loss of heterozygosity on 9p22 was also detected, suggesting that the loss of function of p16 was induced during hepatocarcinogenesis. 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 p16INK4A gene are not frequent, but may play a role in a sub-set of human HCC.
authors: Department of Medicine and Clinical Science, Kyoto University Faculty of Medicine, Japan.
authors: R
authors: R
authors: Kita
authors: N
authors: N
authors: Nishida
authors: Y
authors: Y
authors: Fukuda
authors: H
authors: H
authors: Azechi
authors: Y
authors: Y
authors: Matsuoka
authors: T
authors: T
authors: Komeda
authors: T
authors: T
authors: Sando
authors: K
authors: K
authors: Nakao
authors: K
authors: K
authors: Ishizaki
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000235:genetics*; D005091:Exons; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D011518:Proto-Oncogene Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases