Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer
Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer
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DOI：
10.1093/hmg/ddq351
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发表时间：
2010-11-01
影响因子：
3.5
通讯作者：
Kang, Daehee
中科院分区：
文献类型：
--
作者：
Li, Lian;Lee, Kyoung-Mu;Kang, Daehee
DNA甲基化是发生在癌发生早期阶段的主要表观遗传修饰。我们进行了全基因组 DNA 甲基化分析，以评估乳腺癌雌激素受体 (ER) 和孕激素受体 (PR) 状态中的 DNA 甲基化状态是否不同。从首尔乳腺癌研究的生物样本库中选择 12 个 ER+/PR+ 和 12 个 ER-/PR- 乳腺癌组织进行 Infinium 甲基化测定。通过Student's t检验评估两组之间14 000个基因的27 578个甲基化位点的DNA甲基化状态的差异。估计错误发现率（FDR）以评估假阳性关联的概率。在 27 578 个位点中，148 个位点（0.54%）在 ER+/PR+ 和 ER-/PR- 乳腺癌之间存在显着差异（P < 0.001）； 93 个高甲基化，55 个低甲基化。五个基因，FAM124B (P = 7.26 x 10(-7))、MANEAL (P = 3.38 x 10(-7))、ST6GALNAC1 (P = 2.85 x 10(-6))、NAV1 (P = 5.94 x 10(-6)) 和 PER1 (P = 6.45 x 10(-6)) 在处理后仍然显着。多次测试的校正（FDR < 0.05）。在随后对五个基因的复制研究中，五个基因中的四个得到了验证；在 ER+/PR+ 乳腺癌中，FAM124B 和 ST6GALNAC1 显着高甲基化，NAV1 和 PER1 显着低甲基化（P < 0.05）。在首次根据乳腺癌受体状态进行的全基因组DNA甲基化分析中，我们发现ER/PR状态影响乳腺癌中FAM124B、ST6GALNAC1、NAV1和PER1的DNA甲基化状态。
DNA methylation is the main epigenetic modification that occurs at the early stages of carcinogenesis. We performed a genome-wide DNA methylation profiling to evaluate whether the DNA methylation state is different in the estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. Twelve ER+/PR+ and 12 ER-/PR- breast cancer tissues were selected from the biorepository of the Seoul Breast Cancer Study for Infinium Methylation Assay. The difference of the DNA methylation state of 27 578 methylation sites in 14 000 genes between two groups was evaluated by Student's t-test. False discovery rate (FDR) was estimated to evaluate the probability of false positive associations. Of the 27 578 sites, 148 sites (0.54%) were significantly different between ER+/PR+ and ER-/PR- breast cancers (P < 0.001); 93 hypermethylated and 55 hypomethylated. Five genes, FAM124B (P = 7.26 x 10(-7)), MANEAL (P = 3.38 x 10(-7)), ST6GALNAC1 (P = 2.85 x 10(-6)), NAV1 (P = 5.94 x 10(-6)) and PER1 (P = 6.45 x 10(-6)) remained significant after correction for multiple tests (FDR < 0.05). In a subsequent replication study for five genes, four of the five genes were validated; FAM124B and ST6GALNAC1 were significantly hypermethylated, and NAV1 and PER1 were significantly hypomethylated in ER+/PR+ breast cancers (P < 0.05). In the first genome-wide DNA methylation profiling according to the receptor status of breast cancer, we found that ER/PR status affects the DNA methylation state of FAM124B, ST6GALNAC1, NAV1 and PER1 in breast cancer.