Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers
Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers
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DOI：
10.1038/sj.onc.1205402
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发表时间：
2002-04-04
期刊：
影响因子：
8
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Mizuno, K;Osada, H;Takahashi, T
CHFR基因最近被scholnick和Halazonetis克隆，以寻找具有叉头关联基序的新型有丝分裂检查点基因，该基因被认为在有丝分裂前期检查点中发挥关键作用。在这项研究中，我们证实了CHFR基因启动子区域的肿瘤特异性异常高甲基化在很大一部分肺癌中与CHFR转录本可检测水平的缺失相关。37例原发性肺癌中有7例出现异常高甲基化。用去甲基化剂5-aza-2'-脱氧胞苷处理后，CHFR基因在表现出异常高甲基化和表达缺失的肺癌细胞系中恢复了表达。相比之下，基因改变在肺癌中并不常见。这是首次在任何类型的人类癌症中描述CHFR基因的异常高甲基化，并提供了肺癌中多重检查点改变的进一步证据。
The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene with fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. In this study, we demonstrated tumor-specific aberrant hypermethylation of the promoter region of the CHFR gene in a significant fraction of lung cancers in association with loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was observed in seven of 37 primary lung cancer cases. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored expression of the CHFR gene in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its expression. In contrast, genetic alterations were found to be infrequent in lung cancers. This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer.