p16(INK4) gene mutation and allelic loss of chromosome 9p21-22 in Taiwanese hepatocellular carcinoma

Background: The p16(INK4) (MTS1/CDNK2A) gene, located on chromosome 9p21, i s an inhibitor of cyclin-dependent kinase 4. Various data have shown that i t is frequently inactivated in several types of cell lines and primary huma n cancers. Materials and Methods: Thirty cases with hepatocellular carcinom a were studied for possible p16(INK4) gene mutation in Taiwan. Homozygous d eletion was determined using polymerase chain reaction (PCR). The p16(INK4) gene mutation was first screened by single strand conformation polymorphis m, then direct DNA sequencing was performed an the cases with mobility shif ts. Deletion mapping of chromosome 9p21-22 was also carried out with two po lymorphic microsatellite markers (D9S925 and D9S168) using PCR. Results: On e pf the 30 cases had homozygous deletion at exon 3 of the p16(INK4) gene. Another tumor had altered electrophoresed mobility in exon 2 with G to T tr ansversion in the first nucleotide of codon 61 by direct sequencing causing a stop codon (GAG-->TAG). At the D9S925 and D9S168 loci, six out of 24 (25 %) and three out of 19 (16%) informative cases showed loss of heterozygosit y, respectively. Conclusion: Point mutation and homozygous deletion of the p16(INK4) gene ar e present in a subset of hepalocellular carcinomas in Tai wan. The patterns of the p16(INK4) gene alteration are, however; different from those from other regions. In addition, allelic loss on chromosome 9p21 -22 is not an uncommon event in hepatocellular carcinomas. Therefore, the s ignificance of chromosome 9p loss deserves to be extensively investigated.