Epstein-Barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma

被引:302
作者
Kang, GH
Lee, S
Kim, WH
Lee, HW
Kim, JC
Rhyu, MG
Ro, JY
机构
[1] Seoul Natl Univ, Coll Med, Dept Pathol, Chongno Gu, Seoul 110744, South Korea
[2] Canc Res Inst, Seoul, South Korea
[3] Univ Ulsan, Coll Med, Dept Pathol, Seoul, South Korea
[4] Univ Ulsan, Coll Med, Dept Gen Surg, Seoul, South Korea
[5] Catholic Univ Korea, Coll Med, Dept Microbiol, Seoul, South Korea
关键词
D O I
10.1016/S0002-9440(10)64901-2
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
CpG island methylation is an important mechanism for inactivating the genes involved in tumorigenesis. Gastric carcinoma (GC) is one of the tumors that exhibits a high frequency of aberrant CpG island methylation. There have been many reports suggesting a close link between Epstein-Barr virus (EBV) and the development of GC. However, little is known about the oncogenic mechanism of EBV in gastric carcinogenesis. Twenty-one cases of EBV-positive GC and 56 cases of EBV-negative GC were examined for aberrant DNA methylation of the CpG islands of 19 genes or loci and the differences in the methylation frequency between EBV-positive and -negative GCs were investigated to determine a role of aberrant methylation in EBV-related gastric carcinogenesis. The average number of methylated genes or loci was higher In EBV-positive GCs than in EBV-negative GCs (13.4 versus 7.8, respectively, P < 0.001). EBV-positive GCs showed methylation in at least 10 CpG islands (52.6% of the tested genes), whereas 62.5% of EBV-negative GCs showed methylation in <10 CpG islands. THBS1, APC, p16, 14-3-3 sigma, MINT1, and MINT25 were methylated at a frequency > 90% in EBV-positive GCs. The methylation frequency difference in the respective CpG islands between EBV-positive and -negative GCs was statistically significant (P < 0.05). Among these genes or loci, the methylation frequency of p16 in the EBV-positive GCs was more than three times higher than in the EBV-negative GCs. The PTEN, RASSF1A, GSTP1, MGMT, and MINT2 were methylated in EBV-positive GCs at a frequency of more than three times that of the EBV-negative GCs. These results demonstrate a relationship between EBV and aberrant methylation in GC and suggest that aberrant methylation may be an important mechanism of EBV-related gastric carcinogenesis.
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页码:787 / 794
页数:8
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