Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer.
Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer.
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DOI：
10.3892/or.17.1.41
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发表时间：
2007
期刊：
影响因子：
4.2
通讯作者：
Megumi Yanokura;K. Banno;M. Kawaguchi;N. Hirao;A. Hirasawa;N. Susumu;K. Tsukazaki;D. Aoki
中科院分区：
文献类型：
--
作者：
Megumi Yanokura;K. Banno;M. Kawaguchi;N. Hirao;A. Hirasawa;N. Susumu;K. Tsukazaki;D. Aoki
细胞周期检查点基因的异常甲基化与癌细胞对抗癌药物的敏感性之间的关系是当前感兴趣的问题。在这项研究中，我们研究了子宫内膜癌中CHFR(带叉头和无名指的检查点)有丝分裂检查点基因异常高甲基化与紫杉烷类药物敏感性的关系。甲基化特异性聚合酶链式反应(MSP)在12.0%(6/50)的子宫内膜癌标本中发现CHFR异常高甲基化，提示CHFR异常高甲基化在低分化腺癌(G3)中更为常见(p<；0.05)。在6个培养细胞系中，SNG-II和HEC108细胞出现异常甲基化，CHFR表达降低。这些细胞对紫杉烷类药物高度敏感，但在去甲基化后产生抗药性。CHFR异常高甲基化的癌症标本对紫杉烷也表现出高度的敏感性。据我们所知，这项研究是首次检测CHFR在子宫内膜癌中的异常高甲基化状态，我们的结果表明，CHFR的甲基化状态可能是一个新的分子指标，将使子宫内膜癌的个体化治疗设计成为可能。这在低分化腺癌(G3)中可能尤其重要，众所周知，G3的预后很差。
The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanes in endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFR in 12.0% (6/50) of endometrial cancer specimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p<0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanes but became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFR also exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFR in endometrial cancer, and our results suggest that the methylation status of CHFR may be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.