Promoter hypermethylation of the Chfr gene in neoplastic and non-neoplastic gastric epithelia.
Promoter hypermethylation of the Chfr gene in neoplastic and non-neoplastic gastric epithelia.
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CHFR基因在肿瘤和非塑性胃上皮中的启动子高甲基化。
DOI：
10.1038/sj.bjc.6601849
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发表时间：
2004-05-17
影响因子：
8.8
通讯作者：
Motoyama, T
中科院分区：
文献类型：
--
作者：
Honda, T;Tamura, G;Waki, T;Kawata, S;Nishizuka, S;Motoyama, T
虽然染色体不稳定性是人类实体瘤的一个共同特征，但尚未发现有丝分裂检查点相关基因的异常。然而，最近，Chfr（checkpoint with forkhead associated and ring finger），一个有丝分裂应激检查点基因，已经被报道在几种类型的人类恶性肿瘤中由于启动子超甲基化而失活。为了阐明Chfr基因启动子甲基化是否参与胃癌的发生，我们研究了胃癌细胞系和原发性胃癌中Chfr基因启动子甲基化状态。同时，我们还检测了来自患癌和非患癌胃的非肿瘤性胃上皮细胞的Chfr启动子超甲基化，以研究其癌症特异性。10株胃癌细胞系中有2株（20%）出现Chfr基因启动子高甲基化并导致表达缺失，经5-aza-2′-deoxycytidine处理后可恢复。Chfr启动子甲基化存在于35%（25/71）的原发性肿瘤中，并且在早期和晚期阶段以相似的频率发生。至于非肿瘤性胃上皮，1%（91例中的1例）来自非癌胃，5%（71例中的4例）来自癌胃，表现出Chfr启动子高甲基化。因此，Chfr启动子超甲基化主要是癌症特异性的，并且经常导致胃癌中的染色体不稳定性。
While chromosomal instability is a common feature of human solid tumours, no abnormalities in genes involved in the mitotic checkpoint have been identified. However, recently, Chfr (checkpoint with forkhead associated and ring finger), a mitotic stress checkpoint gene, has been reported to be inactivated due to promoter hypermethylation in several types of human malignancy. To clarify whether Chfr promoter hypermethylation is involved in gastric carcinogenesis, we investigated the promoter methylation status of the Chfr gene in gastric cancer cell lines and primary gastric cancers. Non-neoplastic gastric epithelia from cancer-bearing and noncancer-bearing stomachs were also examined for Chfr promoter hypermethylation to study its cancer specificity. Two of 10 gastric cancer cell lines (20%) showed Chfr promoter hypermethylation with resultant loss of expression, which could be restored by 5-aza-2′ deoxycytidine treatment. Chfr promoter hypermethylation was present in 35% (25 of 71) of primary tumours and occurred at similar frequencies in early and advanced stages. As for non-neoplastic gastric epithelia, 1% (one of 91) from noncancer-bearing and 5% (four of 71) from cancer-bearing stomachs exhibited Chfr promoter hypermethylation. Thus, Chfr promoter hypermethylation is mostly cancer specific and frequently leads to chromosome instability in gastric cancer.
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影响因子：
64.8
作者：
Cahill, DP;Lengauer, C;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
5.7
作者：
Waki, T;Tamura, G;Motoyama, T
通讯作者：
Motoyama, T
影响因子：
8
作者：
Waki, T;Tamura, G;Motoyama, T
通讯作者：
Motoyama, T
影响因子：
8
作者：
Mizuno, K;Osada, H;Takahashi, T
通讯作者：
Takahashi, T
影响因子：
8.8
作者：
Satoh, A;Toyota, M;Itoh, F;Kikuchi, T;Obata, T;Sasaki, Y;Suzuki, H;Yawata, A;Kusano, M;Fujita, M;Hosokawa, M;Yanagihara, K;Tokino, T;Imai, K
通讯作者：
Imai, K