Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
Hum Mol Genet. 2010 Nov 1;19(21):4273-7. doi: 10.1093/hmg/ddq351. Epub 2010 Aug 19.
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 × 10(-7)), MANEAL (P = 3.38 × 10(-7)), ST6GALNAC1 (P = 2.85 × 10(-6)), NAV1 (P = 5.94 × 10(-6)) and PER1 (P = 6.45 × 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.
DNA 甲基化是致癌作用早期发生的主要表观遗传修饰。我们进行了全基因组 DNA 甲基化谱分析，以评估乳腺癌中雌激素受体（ER）和孕激素受体（PR）状态的 DNA 甲基化状态是否不同。从首尔乳腺癌研究生物库中选择了 12 例 ER+/PR+和 12 例 ER-/PR-乳腺癌组织，用于 Infinium 甲基化分析。通过 Student's t 检验评估两组之间 14000 个基因中的 27578 个甲基化位点的 DNA 甲基化状态差异。估计错误发现率（FDR）以评估假阳性关联的概率。在 27578 个位点中，有 148 个（0.54%）在 ER+/PR+和 ER-/PR-乳腺癌之间存在显著差异（P < 0.001）；93 个高甲基化和 55 个低甲基化。五个基因，FAM124B（P = 7.26×10(-7)），MANEAL（P = 3.38×10(-7)），ST6GALNAC1（P = 2.85×10(-6)），NAV1（P = 5.94×10(-6)）和 PER1（P = 6.45×10(-6)）在经过多次检验校正（FDR<0.05）后仍然显著。在对五个基因的后续复制研究中，五个基因中的四个得到了验证；FAM124B 和 ST6GALNAC1 在 ER+/PR+乳腺癌中显著高甲基化，而 NAV1 和 PER1 则显著低甲基化（P < 0.05）。在根据乳腺癌受体状态进行的首次全基因组 DNA 甲基化谱分析中，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。
