Alterations of CDKN2(p16/MTS1) exon 2 in human hepatocellular carcinoma

To determine the state of CDKN2(p16/MTS1) gene in human hepatocellular carcinoma (HCC), the polymerase chain reaction (PCR), dot blot hybridization, PCR-single-strand conformation polymorphism (SSCP) and DNA sequencing techniques were applied to investigate the homozygous deletions and intragenic mutations of CDKN2 exon 2 in tumor and non-tumor liver tissues from 24 patients with HCCs. Alterations of CDKN2 exon 2 were found in 10 (2 homozygous deletions and 8 intragenic mutations) of the 24 tumor samples (41.7%), no alteration was found in any of the non-tumor liver tissues. All of the intragenic mutations were located at codon 81 of CDKN2 with GC bases deletions confirmed by DNA sequencing. A different sequence at codon 53-54 (C-G rather than G-C) was also found in all of the liver and tumor tissues. Our study indicates that alterations of CDKN2 gene is not a rare phenomenon in HCC, however, it might play an important role in the development of HCC and codon 81 might be a mutational hotspot of CDKN2 gene in HCC.