Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer.
Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer.
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DOI：
10.1186/s13148-015-0135-8
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发表时间：
2015
影响因子：
5.7
通讯作者：
Salhia B
中科院分区：
文献类型：
--
作者：
Legendre C;Gooden GC;Johnson K;Martinez RA;Liang WS;Salhia B
许多临床病理学标准和分子特征已用于将患者分为高风险组和低风险组。目前，仍然没有有效的方法来确定哪些患者在标准乳腺癌治疗后患有微转移性疾病，以及哪些患者最终会出现局部或远处复发。我们研究的目的是确定可用于预测转移性乳腺癌 (MBC) 的循环 DNA 甲基化变化。差异甲基化分析显示，与健康个体 (H) 或无病幸存者 (DFS) 相比，MBC 中约有 5.0 × 106 个差异甲基化 CpG 位点。相比之下，H 和 DFS 之间有很强的相似性。总体而言，MBC 表现出整体低甲基化和局部 CpG 岛 (CPGI) 高甲基化。数据分析确定了 CpG 岛内的 21 个新热点，与 H 或 DFS 相比，MBC 中的差异最为显着。这种对无细胞 (cf) DNA 的公正分析确定了 21 个与 MBC 相关的 DNA 高甲基化热点，并证明了在全基因组水平上区分肿瘤特异性变化与正常来源信号的能力。该特征是一种潜在的基于血液的生物标志物，可以在手术时和/或化疗完成后有利地指示患有微转移性疾病的患者，这些患者具有高复发风险并且可以从额外的治疗中受益。本文的在线版本 (doi:10.1186/s13148-015-0135-8) 包含补充材料，可供授权用户使用。
A number of clinico-pathological criteria and molecular profiles have been used to stratify patients into high- and low-risk groups. Currently, there are still no effective methods to determine which patients harbor micrometastatic disease after standard breast cancer therapy and who will eventually develop local or distant recurrence. The purpose of our study was to identify circulating DNA methylation changes that can be used for prediction of metastatic breast cancer (MBC). Differential methylation analysis revealed ~5.0 × 106 differentially methylated CpG loci in MBC compared with healthy individuals (H) or disease-free survivors (DFS). In contrast, there was a strong degree of similarity between H and DFS. Overall, MBC demonstrated global hypomethylation and focal CpG island (CPGI) hypermethylation. Data analysis identified 21 novel hotspots, within CpG islands, that differed most dramatically in MBC compared with H or DFS. This unbiased analysis of cell-free (cf) DNA identified 21 DNA hypermethylation hotspots associated with MBC and demonstrated the ability to distinguish tumor-specific changes from normal-derived signals at the whole-genome level. This signature is a potential blood-based biomarker that could be advantageous at the time of surgery and/or after the completion of chemotherapy to indicate patients with micrometastatic disease who are at a high risk of recurrence and who could benefit from additional therapy. The online version of this article (doi:10.1186/s13148-015-0135-8) contains supplementary material, which is available to authorized users.