High-density methylation of p14ARF and p16INK4A in Epstein-Barr virus–associated gastric carcinoma

✍ Scribed by Kazuya Sakuma; Ja-Mun Chong; Makoto Sudo; Tetsuo Ushiku; Yoko Inoue; Junji Shibahara; Hiroshi Uozaki; Hideo Nagai; Masashi Fukayama

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: French
• Weight: 135 KB
• Volume: 112
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.20420

✦ Synopsis

Abstract

Promoter hypermethylation of various tumor‐related genes is extremely frequent in gastric carcinoma (GC) associated with Epstein‐Barr virus (EBV). To investigate the significance of the promoter methylation in this type of GC, we examined the methylation densities of the promoter regions of p14^ARF^ and p16^INK4A^ in EBV‐associated (n = 7) and EBV‐negative (n = 14) GC. Bisulfite sequencing demonstrated a high frequency of concurrent methylation of p14^ARF^ and p16^INK4A^ promoter regions in EBVaGC. Methylation was observed in all 29 CpG sites of p14^ARF^ and all 16 sites of p16^INK4A^ with equally high densities. In EBV‐negative GC, the methylation profiles differed between the 2 genes. Promoter methylation was sporadic and variable in p14^ARF^, and only the last position of CpG in p14^ARF^ was methylated at high frequency. High‐density methylation in p16^INK4A^ was observed in a subset of GC, but the first position of CpG was never methylated in EBV‐negative GC. These findings suggest the presence of mechanisms of de novo and maintenance methylation specific to EBVaGC that might be associated with EBV infection. © 2004 Wiley‐Liss, Inc.