Novel markers of gene methylation and expression in breast cancer
Novel markers of gene methylation and expression in breast cancer
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DOI：
10.1134/s0026893307040061
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发表时间：
2007-08-01
影响因子：
1.2
通讯作者：
Strelnikov, V. V.
中科院分区：
文献类型：
--
作者：
Kuznetsova, E. B.;Kekeeva, T. V.;Strelnikov, V. V.
采用优化的甲基化敏感限制性指纹技术寻找肿瘤基因组中差异甲基化的CpG岛，并检测到乳腺癌中受异常表观遗传调控的7个基因：SEMA6B、BIN1、VCPIP1、LAMC3、KCNH2、CACNG4和PSMF1。对于每个基因，在肿瘤和形态完整的配对乳腺组织样本中估计启动子甲基化率和表达变化（N = 100）。 SEMA6B、BIN1 和 LAMC3 的显着甲基化率分别为 38%、18% 和 8%。这些基因在形态完整的乳腺组织中没有甲基化。通过实时 RT-PCR 检测，44-94% 的肿瘤样本中 SEMA6B、BIN1、VCPIP1、LAMC3、KCNH2、CACNG4 和 PSMF1 的表达降低。 SEMA6B 和 LAMC3 最深刻的变化表明这些基因可以包含在乳腺癌诊断的生物标志物组中。最常甲基化的 CpG 岛（SEMA6B、BIN1 和 LAMC3）的精细甲基化图谱为开发这些基因的有效甲基化测试奠定了基础。
An optimized methylation-sensitive restriction fingerprinting technique was used to search for differentially methylated CpG islands in the tumor genome and detected seven genes subject to abnormal epigenetic regulation in breast cancer: SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4, and PSMF1. For each gene, the rate of promoter methylation and changes in expression were estimated in tumor and morphologically intact paired specimens of breast tissue (N = 100). Significant methylation rates of 38, 18, and 8% were found for SEMA6B, BIN1, and LAMC3, respectively. The genes were not methylated in morphologically intact breast tissue. The expression of SEMA6B, BIN1, VCPIP1, LAMC3, KCNH2, CACNG4, and PSMF1 was decreased in 44-94% of tumor specimens by the real-time RT-PCR assay. The most profound changes in SEMA6B and LAMC3 suggest that these genes can be included in biomarker panels for breast cancer diagnosis. Fine methylation mapping of the most frequently methylated CpG islands (SEMA6B, BIN1, and LAMC3) provides a fundamental basis for developing efficient methylation tests for these genes.