DNA methylation profiles of differentiated-type gastric carcinomas with distinct mucin phenotypes
DNA methylation profiles of differentiated-type gastric carcinomas with distinct mucin phenotypes
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DOI：
10.1111/j.1349-7006.2005.00074.x
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发表时间：
2005-08-01
期刊：
影响因子：
5.7
通讯作者：
Yasui, W
中科院分区：
文献类型：
--
作者：
Motoshita, J;Oue, N;Yasui, W
胃癌（GC）根据粘蛋白表达分为四种表型。先前的研究揭示了GC中不同的遗传特征与粘蛋白表型表达的相关性;然而，表观遗传变化（如DNA甲基化）的作用知之甚少。我们检查了GC的表型表达是否与hMLH 1、MGMT、p16（INK 4a）、RAR-β或CDH 1的DNA甲基化相关。采用免疫组化法检测33例分化型胃癌组织中HGM、M-GGMC-1、MUC 2和CD 10的表达。HGM阳性14例（42.4%），M-GGMC-1阳性5例（15.2%），MUC 2阳性15例（45.5%），CD 10阳性18例（54.5%）。亚硫酸氢盐聚合酶链反应和甲基化特异性聚合酶链反应检测到5例（15.2%）hMLH 1、11例（33.3%）MGMT、13例（39.4%）p16（INK 4a）、17例（51.5%）RAR-β和14例（42.4%）CDH 1的DNA甲基化。hMLH 1基因甲基化在MUC 2阴性胃癌中的发生率高于MUC 2阳性胃癌（P = 0.0488，Fisher精确检验）。相反，MGMT在MUC 2阳性GC中比在MUC 2阴性GC中更频繁地甲基化（P = 0.0078，Fisher精确检验）。胃或直肠标记物与p16（INK 4a），RAR-β和CDH 1基因甲基化之间没有相关性。这些结果表明，特定基因的DNA甲基化，如hMLH 1和MGMT，可能参与了GC的独特的表型表达的一部分。
Gastric carcinomas (GC) are classified into four phenotypes according to mucin expression. Previous studies revealed the association of distinct genetic profiles in GC with mucin phenotypic expression; however, the roles of epigenetic changes, such as DNA methylation, are poorly understood. We examined whether the phenotypic expression of GC was associated with DNA methylation of hMLH1, MGMT, p16(INK4a), RAR-beta or CDH1. Expression of HGM, M-GGMC-1, MUC2, and CD10 was analyzed immunohistochemically in 33 advanced GC with differentiated histology. HGM was expressed in 14 (42.4%) cases, M-GGMC-1 in five (15.2%) cases, MUC2 in 15 (45.5%) cases and CD10 in 18 (54.5%) cases. DNA methylation was detected in five (15.2%) cases for hMLH1, 11 (33.3%) cases for MGMT, 13 (39.4%) cases for p16(INK4a), 17 (51.5%) cases for RAR-beta and 14 (42.4%) cases for CDH1 by bisulfite-polymerase chain reaction and methylation-specific polymerase chain reaction. DNA methylation of hMLH1 occurred more frequently in MUC2-negative GC than in MUC2-positive GC (P = 0.0488, Fisher's exact test). In contrast, MGMT was more frequently methylated in MUC2-positive GC than in MUC2-negative GC (P = 0.0078, Fisher's exact test). There was no correlation between gastric or intestinal-markers and methylation of the p16(INK4a), RAR-beta and CDH1 genes. These results indicate that DNA methylation of specific genes, such as hMLH1 and MGMT, may be involved partly in the distinct phenotypic expression of GC.