Identification of 5 novel genes methylated in breast and other epithelial cancers.
Identification of 5 novel genes methylated in breast and other epithelial cancers.
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DOI：
10.1186/1476-4598-9-51
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发表时间：
2010-03-05
期刊：
影响因子：
37.3
通讯作者：
Latif F
中科院分区：
文献类型：
--
作者：
Hill VK;Hesson LB;Dansranjavin T;Dallol A;Bieche I;Vacher S;Tommasi S;Dobbins T;Gentle D;Euhus D;Lewis C;Dammann R;Ward RL;Minna J;Maher ER;Pfeifer GP;Latif F
有几种高通量方法可以识别癌症中的甲基化基因。 我们利用最近开发的一种方法，即 MIRA（甲基化 CpG 岛恢复测定）与 CpG 岛阵列相结合，来识别乳腺癌中表观遗传失活的新基因。使用这种方法，我们鉴定了许多在乳腺癌细胞系中表现出异常 DNA 甲基化的 CpG 岛。结合 COBRA 和亚硫酸氢盐修饰 DNA 测序，我们确认了 5 个在乳腺肿瘤中经常甲基化的新基因； EMILIN2、SALL1、DBC1、FBLN2 和 CIDE-A。原发性乳腺肿瘤的甲基化频率在 25% 到 63% 之间，而匹配的正常乳腺组织 DNA 要么未甲基化，要么与恶性乳腺组织 DNA 相比甲基化频率低得多。此外，在甲基化乳腺癌细胞系中，用去甲基化剂处理后，上述 5 个基因的表达得以恢复。我们已将此分析扩展到其他三种常见的上皮癌（肺癌、结直肠癌、前列腺癌）。我们证明上述基因在这些癌症中表现出不同水平的甲基化。最后也是最重要的是，EMILIN2 的甲基化与乳腺癌较差的临床结果相关，并且与雌激素受体和孕激素受体阳性乳腺癌密切相关。 MIRA 检测与 CpG 岛阵列的结合是一种非常有用的技术，可用于识别癌症基因组中表观遗传失活的基因，并可为早期癌症诊断、预后和表观遗传治疗提供分子标记。
There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay) combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer. Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25% and 63% in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate). We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers. The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.
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影响因子：
15.8
作者：
Chan, Timothy A.;Glockner, Sabine;Yi, Joo Mi;Chen, Wei;Van Neste, Leander;Cope, Leslie;Herman, James G.;Velculescu, Victor;Schuebel, Kornel E.;Ahuja, Nita;Baylin, Stephen B.
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Baylin, Stephen B.
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Dabelsteen, E
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作者：
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通讯作者：
Colombatti, Alfonso
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作者：
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通讯作者：
Knowles, MA
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P