Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer
Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer
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DOI：
10.1093/annonc/mdn409
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发表时间：
2008-11-01
影响因子：
50.5
通讯作者：
van Diest, P. J.
中科院分区：
文献类型：
--
作者：
Suijkerbuijk, K. P. M.;Fackler, M. J.;van Diest, P. J.
背景：启动子甲基化是乳腺癌发生过程中抑制肿瘤抑制基因表达的一种常见的表观遗传学机制。我们研究了BRCA 1相关的乳腺肿瘤是否显示出与散发性肿瘤相似的癌症预测甲基化模式。11个乳腺癌相关基因甲基化特异性定量多重PCR检测（RARB、RASSF1、TWIST1、CCND2、ESR1、SCGB3A1、BRCA1、BRCA2、CDKN2A、APC、结果：BRCA 1基因甲基化程度随年龄增长而增加（P < 0.001）;所有研究基因的中位累积甲基化指数（CMI）在肿瘤（89）中显著高于正常组织（13，P < 0.001）。BRCA 1相关性乳腺肿瘤（59）的中位CMI显著低于散发性乳腺肿瘤（122，P = 0.001），雌激素受体（ER）阴性肿瘤（73）显著低于ER阳性肿瘤（122，P = 0.005），淋巴结阴性肿瘤（77）显著低于淋巴结阳性肿瘤（137，P = 0.007）。在亚组分析中，BRCA 1生殖系突变对甲基化的影响被证明是独立的ER状态，淋巴结状态和age.Conclusions：这些数据表明，BRCA 1相关的乳腺癌显示较少的启动子甲基化相比，散发性乳腺癌表明疾病病因的差异。
Background: Promoter methylation is a common epigenetic mechanism to silence tumor suppressor genes during breast cancer development. We investigated whether BRCA1-associated breast tumors show cancer-predictive methylation patterns similar to those found in sporadic tumors.Patients and methods: Quantitative multiplex methylation-specific PCR of 11 genes involved in breast carcinogenesis (RARB, RASSF1, TWIST1, CCND2, ESR1, SCGB3A1, BRCA1, BRCA2, CDKN2A, APC, CDH1) was carried out on 32 BRCA1-associated and 46 sporadic breast carcinomas and on normal breast tissue from seven BRCA1 mutation carriers and 13 non-carriers.Results: The extent of cumulative methylation increased with age (P < 0.001). The median cumulative methylation index (CMI) of all studied genes was significantly higher in tumors (89) than in normal tissue (13, P < 0.001). The median CMI was significantly lower in BRCA1-associated (59) than in sporadic breast tumors (122, P = 0.001), in estrogen receptor (ER)-negative tumors (73) than in ER-positive tumors (122, P = 0.005) and in lymph node-negative (77) compared with lymph node-positive tumors (137, P = 0.007). In subgroup analysis, the effect of a BRCA1 germline mutation on methylation proved to be independent of ER status, lymph node status and age.Conclusions: These data indicate that BRCA1-associated breast cancers show less promoter methylation compared with sporadic breast carcinomas indicating a difference in disease etiology.