前列腺癌的转移至罕见部位，如脑部，正因治疗的改善使人们寿命更长而变得更为常见。表观遗传分析方面是原发性前列腺癌的一个特征，已证明不同的DNA甲基化谱与相互排斥的SPOP突变或TMPRSS2-ERG融合基因背景有关。我们使用来自42位患者的前列腺癌脑转移瘤（PCBM）进行DNA甲基化分析，其中17位患者的原发瘤与之匹配。这项研究旨在研究原发性前列腺癌和PCBM之间的表观遗传差异、表观遗传变异与突变背景之间的关系以及可能与PCBM有关的特定表观遗传变异。PCBM的多区域采样揭示了转移瘤内的表观稳定性。PCBM的异常甲基化与突变背景和PRC2复合体活性有关，在SPOP突变的PCBM中尤其显著。虽然PCBM表现出CpG岛高甲基化表型，但在神经活性配体-受体相互作用和细胞粘着分子（如GABRB3、CLDN8和CLDN4）的启动子中也观察到低甲基化，这表明来自原发性肿瘤的细胞可能需要特定的重编程来形成脑转移瘤。该研究揭示了PCBM的DNA甲基化景观和PCBM相关异常DNA甲基化的潜在机制和影响。

Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy resulting from improved treatments. Epigenetic dysregulation is a feature of primary prostate cancer, and distinct DNA methylation profiles have been shown to be associated with the mutually exclusive SPOP mutant or TMPRSS2-ERG fusion genetic backgrounds. Using a cohort of prostate cancer brain metastases (PCBM) from 42 patients, with matched primary tumors for 17 patients, we carried out a DNA methylation analysis to examine the epigenetic distinction between primary prostate cancer and PCBM, the association between epigenetic alterations and mutational background, and particular epigenetic alterations that may be associated with PCBM. Multiregion sampling of PCBM revealed epigenetic stability within metastases. Aberrant methylation in PCBM was associated with mutational background and PRC2 complex activity, an effect that is particularly pronounced in SPOP mutant PCBM. While PCBM displayed a CpG island hypermethylator phenotype, hypomethylation at the promoters of genes involved in neuroactive ligand-receptor interaction and cell adhesion molecules such as GABRB3, CLDN8, and CLDN4 was also observed, suggesting that cells from primary tumors may require specific reprogramming to form brain metastasis. This study revealed the DNA methylation landscapes of PCBM and the potential mechanisms and effects of PCBM-associated aberrant DNA methylation.