Concordance of DNA methylation profiles between breast core biopsy and surgical excision specimens containing ductal carcinoma in situ (DCIS)

Whether DNA methylation in ductal carcinoma in situ (DCIS), measured in core biopsy and surgical specimens are similar, remains unclear. Here, we compared genome-scale DNA methylation measured in matched core biopsy and surgical specimens from DCIS, including specific DNA methylation biomarkers of subsequent invasive cancer. This study aims to compare genome-scale DNA methylation between core biopsies (in this GEO accession) and surgical specimens (previously published in GSE66313; see Overall Design below). Within-subject variability in DNA methylation was significantly lower than between-subject variability (all P < 2.20E-16). In 641 CpGs whose methylation was related with increased hazard of invasive breast cancer, lower within-subject than between-subject variability was observed in 92.3% of the study participants (P < 0.05). Between patient-matched core biopsy and surgical specimens, < 0.6% of CpGs measured had changes in median DNA methylation > 15%, and a pathway analysis of these CpGs indicated enrichment for genes related with wound healing. Our results indicate that DNA methylation measured in core biopsies are representative of the matched surgical specimens and suggest that DCIS biomarkers measured in core biopsies can inform clinical decision-making. We compared genome-scale DNA methylation of 13 breast DCIS core biopsy samples (this accession) with previously published, matched surgical specimens (GSE66313).

目前尚不明确在核心穿刺活检标本与手术切除标本中检测的导管原位癌（ductal carcinoma in situ, DCIS）的DNA甲基化水平是否一致。本研究针对DCIS患者的配对核心穿刺活检标本与手术切除标本开展全基因组DNA甲基化水平检测对比，其中包含与后续侵袭性癌症相关的特异性DNA甲基化生物标志物。本研究旨在对比核心穿刺活检标本（对应本GEO数据集收录样本）与手术切除标本（此前已发表于GSE66313；详见下文总体研究设计）的全基因组DNA甲基化水平。受试者内部的DNA甲基化变异度显著低于受试者间的变异度（所有P值均<2.20×10^-16）。在641个甲基化水平与浸润性乳腺癌风险升高相关的CpG位点中，92.3%的研究对象呈现出受试者内部变异度低于受试者间变异度的特征（P<0.05）。在配对的核心穿刺活检标本与手术切除标本之间，仅<0.6%的检测CpG位点的DNA甲基化中位数变化幅度超过15%；针对这些位点的通路分析显示，其关联基因显著富集于伤口愈合相关通路。本研究结果表明，核心穿刺活检标本的DNA甲基化检测结果可代表配对手术切除标本的相应水平，同时提示通过核心穿刺活检标本检测得到的DCIS生物标志物可为临床决策提供参考依据。本研究对比了13例乳腺DCIS核心穿刺活检标本（对应本数据集收录样本）与此前已发表的配对手术切除标本（GSE66313）的全基因组DNA甲基化水平。