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High‐density methylation of p14 ARF and p16 INK4A in Epstein‐Barr virus–associated gastric carcinoma
Author(s) -
Sakuma Kazuya,
Chong JaMun,
Sudo Makoto,
Ushiku Tetsuo,
Inoue Yoko,
Shibahara Junji,
Uozaki Hiroshi,
Nagai Hideo,
Fukayama Masashi
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20420
Subject(s) - methylation , cpg site , biology , dna methylation , bisulfite sequencing , promoter , cancer research , microbiology and biotechnology , bisulfite , gene , genetics , gene expression
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.