Department of Clinical Genetics, University Hospital of Southern Denmark, Beriderbakken 4, 7100, Vejle, Denmark.
Department of Gynecology and Obstetrics, Medical School, São Paulo State University (UNESP), Botucatu, SP, 18618-687, Brazil.
Clin Epigenetics. 2024 Jul 6;16(1):89. doi: 10.1186/s13148-024-01695-x.
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.
炎性乳腺癌（IBC）是一种罕见疾病，其特征为快速进展、早期转移和高死亡率。
从 140 例病例队列中选择 24 例 IBC 进行全基因组 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）。
我们鉴定出 46908 个差异甲基化位置（DMP）（66%呈低甲基化）；CpG 岛主要呈高甲基化（39.9%）。无监督聚类分析显示，DMP 存在三个聚类，其特征为特定基因突变和激素受体状态的富集。DNA 甲基化发现与外部数据集（TCGA-BRCA 分期 III-IV）的比较产生了 385 个共享 DMP，映射到 333 个基因（264 个呈高甲基化）。151 个 DMP 与 110 个基因相关，这些基因在 IBC 中检测到差异表达（GSE45581），68 个 DMP 与基因表达呈负相关。我们还鉴定出 4369 个已知基因上的差异甲基化区域（DMR）（2392 个呈低甲基化）。在 31 例 IBC 样本中，选择 BCAT1、CXCL12 和 TBX15 基因座并通过亚硫酸氢盐焦磷酸测序进行评估。与非三阴性相比，三阴性中 BCAT1 和 TBX15 的甲基化水平更高，而 CXCL12 的甲基化水平更低。TBX15 的甲基化水平与肥胖有关。
我们的研究结果揭示了一种具有潜在功能 DMP 和 DMR 的异质性 DNA 甲基化图谱。这些 DNA 甲基化数据为预后分层和治疗选择提供了有价值的见解，以改善患者的预后。
Zotero 插件
