Association between frequent CpG island methylation and HER2 amplification in human breast cancers.
Association between frequent CpG island methylation and HER2 amplification in human breast cancers.
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DOI：
10.1093/carcin/bgp021
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发表时间：
2009-03
期刊：
影响因子：
4.7
通讯作者：
K. Terada;E. Okochi‐Takada;S. Akashi-Tanaka;K. Miyamoto;K. Taniyama;H. Tsuda;Kiyoshi Asada;M. Kaminishi;T. Ushijima
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文献类型：
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作者：
K. Terada;E. Okochi‐Takada;S. Akashi-Tanaka;K. Miyamoto;K. Taniyama;H. Tsuda;Kiyoshi Asada;M. Kaminishi;T. Ushijima
CpG岛（CpG island methylator phenotype）的频繁甲基化，在某些癌症中被称为CpG岛甲基化表型（CpG island methylator phenotype），与个体肿瘤类型中不同的临床病理特征（包括基因扩增）相关。人乳腺癌中HER2扩增是一个重要的预后和治疗靶点，但HER2扩增与频繁的CGI甲基化之间的关系尚不清楚。为了澄清这种关联，我们在这里量化了63例人类乳腺癌中11个基因的启动子cgi的甲基化水平，这些基因不太可能赋予细胞生长优势。一种癌症中甲基化基因的数量不服从双峰分布，63例癌症被分为频繁甲基化（n = 16）、中度甲基化（n = 26）和非甲基化（n = 21）。HER2扩增的发生率在频繁甲基化的癌症中（16例中有11例）明显高于未甲基化的癌症（21例中有2例，P = 0.001）。此外，甲基化基因数量与HER2扩增程度相关（r = 0.411, P = 0.002）。临床病理特征与CDKN2A、BRCA1和CDH1甲基化的相关性分析显示，频繁的甲基化与较高的核分级有显著相关性（P = 0.001）。这些结果表明，频繁的甲基化与乳腺癌中HER2扩增密切相关，并表明频繁的甲基化可能是部分人类乳腺癌中各种特征的决定因素。
The presence of frequent methylation of CpG islands (CGIs), designated as the CpG island methylator phenotype in some cancers, is associated with distinct clinicopathological characteristics, including gene amplification, in individual tumor types. Amplification of HER2 in human breast cancers is an important prognostic and therapeutic target, but an association between HER2 amplification and frequent CGI methylation is unknown. To clarify the association, we here quantified methylation levels of promoter CGIs of 11 genes, which are unlikely to confer growth advantage to cells, in 63 human breast cancers. The number of methylated genes in a cancer did not obey a bimodal distribution, and the 63 cancers were classified into those with frequent methylation (n = 16), moderate methylation (n = 26) and no methylation (n = 21). The incidence of HER2 amplification was significantly higher in the cancers with frequent methylation (11 of 16) than in those with no methylation (2 of 21, P = 0.001). Also, the number of methylated genes correlated with the degree of HER2 amplification (r = 0.411, P = 0.002). Correlation analysis with clinicopathological characteristics and methylation of CDKN2A, BRCA1 and CDH1 revealed that frequent methylation had significant correlation with higher nuclear grades (P = 0.001). These showed that frequent methylation had a strong association with HER2 amplification in breast cancers and suggested that frequent methylation can be a determinant of various characteristics in a fraction of human breast cancers.