炎性乳腺癌（IBC）是一种罕见疾病，具有进展快、转移早、死亡率高的特点。进行了全基因组DNA甲基化分析（EPIC BeadChip平台，Illumina）和体细胞基因变异（105个癌症相关基因）在从 140 个病例队列中选出的 24 个 IBC 中。我们鉴定了 46,908 个 DMP（差异甲基化位置）（66% 低甲基化）； CpG 岛主要高度甲基化 (39.9%)。无监督聚类分析揭示了三个 DMP 簇，其特征是特定基因突变和激素受体状态的富集。 DNA 甲基化结果与外部数据集（TCGA-BRCA III-IV 期）之间的比较得出了 333 个基因（264 个超甲基化）中映射的 385 个共享 DMP。 151 个 DMP 与先前在 IBC 中检测为差异表达的 110 个基因 (GSE45581) 相关，68 个 DMP 与基因表达呈负相关。我们还确定了映射到已知基因（2392 个低甲基化）的 4369 个 DMR（差异甲基化区域）。通过亚硫酸氢盐焦磷酸测序在 31 个 IBC 样品中选择和评估 BCAT1、CXCL12 和 TBX15 位点。与非三阴性 IBC 病例相比，三阴性 IBC 病例中 BCAT1 和 TBX15 的甲基化水平较高，而三阴性 IBC 病例中 CXCL12 的甲基化水平较低。 TBX15 甲基化水平与肥胖相关。我们的研究结果揭示了具有潜在功能性 DMP 和 DMR 的异质 DNA 甲基化谱。 DNA 甲基化数据为预后分层和治疗选择提供了宝贵的见解，以改善患者的治疗结果。© 2024。作者。

Inflammatory breast cancer (IBC) is a rare disease characterized by rapid progression, early metastasis, and a high mortality rate.Genome-wide DNA methylation analysis (EPIC BeadChip platform, Illumina) and somatic gene variants (105 cancer-related genes) were performed in 24 IBCs selected from a cohort of 140 cases.We identified 46,908 DMPs (differentially methylated positions) (66% hypomethylated); CpG islands were predominantly hypermethylated (39.9%). Unsupervised clustering analysis revealed three clusters of DMPs characterized by an enrichment of specific gene mutations and hormone receptor status. The comparison among DNA methylation findings and external datasets (TCGA-BRCA stages III-IV) resulted in 385 shared DMPs mapped in 333 genes (264 hypermethylated). 151 DMPs were associated with 110 genes previously detected as differentially expressed in IBC (GSE45581), and 68 DMPs were negatively correlated with gene expression. We also identified 4369 DMRs (differentially methylated regions) mapped on known genes (2392 hypomethylated). BCAT1, CXCL12, and TBX15 loci were selected and evaluated by bisulfite pyrosequencing in 31 IBC samples. BCAT1 and TBX15 had higher methylation levels in triple-negative compared to non-triple-negative, while CXCL12 had lower methylation levels in triple-negative than non-triple-negative IBC cases. TBX15 methylation level was associated with obesity.Our findings revealed a heterogeneous DNA methylation profile with potentially functional DMPs and DMRs. The DNA methylation data provided valuable insights for prognostic stratification and therapy selection to improve patient outcomes.© 2024. The Author(s).