Genetic Alterations of p16Ink4A and p15Ink4B in Gastric Carcinomas / 대한암학회지

ABSTRACT

PURPOSE: p16Ink4A and p15lnk4B, encoded by the genes located on chromosome 9p21, are cyclin-dependent kinase 4 inhibitors and are the upstream regulators of pRB (retinoblastoma protein) function and are involved in the regulation of cell cycle in mammalian cells. It has been demonstrated that p16 and p15 genes are frequently deleted, mutated, and hypermethylated in many malignancies and cancer cell lines. This study was performed to investigate the genetic alteration and immunohistochemical profile of p16 and p15 in gastric carcinomas. MATERIALS AND METHODS: We examined 30 primary gastric cancer samples using PCR- SSCP (Polymerase chain reaction-single strand conformation polymorphism), DNA sequencing, PCR-based hypermethylation assay, and immunohistochemistry. RESULTS: No homozygous deletion was detected in either pl6 or p15 gene, and only one gastric carcinoma sample showed mutation of p16 gene and p15 gene. However, hyper-methylation of 5' CpG islands was observed in 53.6% of exon1 of p16 gene and in 46.4% of exon 1 of pl5 gene. By immunohistochemistry of p16, nuclear under-expression was observed in 58.6%, whereas nuclear over-expression was detected in 31% of formalin-fixed, paraffin-embedded gastric cancer tissues. CONCLUSIONS: Our results suggest that the p16 and p15 tumor suppressor genes may play an important role in gastric carcinogenesis and may be inactivated not by deletions or mutations but mainly by hypermethylation of their 5' CpG islands. There was a good correlation between methylation study and immunohistochemical results in p16 genes.