BJC：CACNA2D3基因甲基化可预测乳腺癌扩散风险

在一项新研究中，给一个癌基因加上一种分子“便利贴(post-it note)”能够预测患者乳腺癌扩散的风险。

来自英国伦敦帝国学院(Imperial College London)的英国癌症研究中心研究人员证实CACNA2D3基因上高水平的被称作甲基化的分子修饰与乳腺癌患者体内这种疾病的扩散相关联。2012年7月10日，相关研究成果发表在British Journal of Cancer期刊上。

已知基因CACNA2D3是一个阻止癌症产生的肿瘤抑制基因。在健康的乳腺细胞中，它并未甲基化，但是在乳腺癌细胞中，它是高度甲基化的。甲基化是一种常见的细胞过程：将甲基加到DNA上以便阻止基因表达，即在DNA上就像便利贴那样告诉细胞何时关闭基因表达。

这项研究揭示加入甲基基团到CACNA2D3基因上将阻止它发挥抵抗癌症产生的作用。已知这个基因在诸如肺癌、肾细胞癌、神经母细胞瘤(neuroblastoma)和骨肉瘤(osteosarcoma)之类的多种癌症中存在缺陷或缺失，但是这项研究是首次将它与乳腺癌关联在一起。

论文第一作者Carlo Palmieri博士说，“我们的研究提示着甲基基团能够抑制CACNA2D3基因传递的信息：阻断它抵抗乳腺癌的潜在保护性作用。这个基因的甲基化可能能够被用来预测哪些乳腺癌患者有更大的可能性发生癌症扩散，从而有助于医生们决定哪些治疗策略将是最为效果的。”

下一阶段将是在更大的研究中重复这些发现以便证实分析这个基因的甲基化是否是一种有效的测试。

本文编译自'Post-it note' on breast cancer gene signals risk of disease spreading

doi:10.1038/bjc.2012.231
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Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas

C Palmieri, B Rudraraju, M Monteverde, L Lattanzio, O Gojis, R Brizio, O Garrone, M Merlano, N Syed, C Lo Nigro and T Crook

Background: Calcium is an important intracellular messenger that mediates many biological processes that are relevant to the malignant process. Calcium ion channels are key in controlling the intracellular calcium, and little is known about their role in human cancer. Methods: We used qPCR and pyrosequencing to investigate expression and epigenetic regulation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) in breast cancer cell lines, primary cancers and metastatic lesions. Results: Expression of CACNA2D3 mRNA is regulated in breast cancer cell lines by methylation in the CpG island located in the 5′ regulatory region of the gene. Expression is upregulated by azacytidine (AZA) in cells with CpG island methylation but unaffected in cells lacking methylation. In primary breast carcinomas, methylation is more common in cancers, which subsequently relapse with loco-regional and, particularly, visceral metastatic disease in both oestrogen receptor-α (ER)-positive and -negative cases. Furthermore, CACNA2D3 CpG island is frequently methylated in breast cancer that has metastasised to the central nervous system. Conclusion: Methylation-dependent transcriptional silencing of CACNA2D3 may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease.