p73 gene promoter methylation in Epstein-Barr virus-associated gastric carcinoma

被引:82
|
作者
Ushiku, Tetsuo
Chong, Ja-Mun
Uozaki, Hiroshi
Hino, Rumi
Chang, Moon-Sung
Sudo, Makoto
Rani, Barua Rita
Sakuma, Kazuya
Nagai, Hideo
Fukayama, Masashi
机构
[1] Univ Tokyo, Grad Sch Med, Dept Pathol, Bunkyo Ku, Tokyo 1130033, Japan
[2] Yamanashi Univ, Dept Surg, Yamanashi, Japan
[3] Jichi Med Sch, Dept Surg, Tochigi, Japan
关键词
gastric carcinoma; Epstein-Barr virus; CpG island methylation; p73;
D O I
10.1002/ijc.22275
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To clarify the significance of p73 in Epstein-Barr virus (EBV)-associated gastric carcinoma (GC), the immunohistochemical expression and CpG-island methylation of p73 were evaluated in cancer tissues and adjacent nonneoplastic tissues of GC with and without EBV infection. Loss of p73 expression by immunohistochemistry was specific to EBV-associated GC (11/13) compared to EBV-negative GC (3/38), which was independent of abnormal p53 expression. With methylation-specific polymerase chain reaction (MSP), the aberrant methylation of p73 exon 1 was similarly specific to EBV-associated GC (12/13), and also rare in EBV-negative GC (2/38). Bisulfite sequencing for p73 exon 1 and its 5' region confirmed the MSP results, showing uniform and high-density methylation in EBV-associated GC. Comparative MSP analysis of p14, p16 and p73 methylation, using 20 cases each of formalin-fixed and paraffin-embedded tissues of early GC with and without EBV infection, confirmed 2 types of methylation: global methylation with increased rates (p14 and p16) and specific methylation of p73 in EBV-associated GC. In nonneoplastic mucosa, p14, p16 and p73 methylation occurred in both EBV-associated (8/33, 6/34 and 3/38, respectively) and EBV-negative GC (6/23, 4/35, and 1/35). p73 methylation was observed in the mucosa without H. pylori infection in all 4 samples. Loss of p73 expression through aberrant methylation of the p73 promoter occurs specifically in EBV-associated GC, together with the global methylation of p14 and p16. A specific type of gastritis, prone to a higher grade of atrophy and p73 methylation, may facilitate the development of EBV-associated GC. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:60 / 66
页数:7
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