DNA methylome of familial breast cancer identifies distinct profiles defined by mutation status. Homo sapiens

It is now well understood that epigenetic alterations occur frequently in sporadic breast carcinogenesis, but little is known about the epigenetic alterations associated with familial breast tumors. We performed genome-wide DNA methylation profiling on familial breast cancers (n=33) to identify patterns of methylation specific to the different mutation groups (BRCA1, BRCA2 and BRCAx) or intrinsic subtypes of breast cancer (basal, luminal A, luminal B, HER2 and normal-like). We used methylated DNA immunoprecipitation (meDIP) on Affymetrix human promoter chips to interrogate methylation profiles across 25,500 distinct transcripts. Overall design: MeDIP of familial breast tumor DNA ("b"=MeC antibody bound) compared to input DNA ("i" = input) for each sample

目前学界已明确，表观遗传改变在散发性乳腺癌发生过程中频繁出现，但与家族性乳腺肿瘤相关的表观遗传改变仍鲜为人知。我们对33例家族性乳腺癌样本开展全基因组DNA甲基化谱分析，旨在挖掘不同突变组别（BRCA1、BRCA2及BRCAx）或乳腺癌固有亚型（基底型、管腔A型、管腔B型、HER2过表达型及正常样型）特异性的甲基化模式。我们采用甲基化DNA免疫沉淀（methylated DNA immunoprecipitation, meDIP）技术结合Affymetrix人类启动子芯片，对25500个不同转录本的甲基化谱进行检测。实验整体设计：针对每一例样本，将家族性乳腺肿瘤DNA的甲基化DNA免疫沉淀富集产物（标记为"b"，即结合甲基化胞嘧啶抗体的组分）与输入DNA（标记为"i"，即初始输入样本）进行比对分析。