breast cancer brain  (AcceGen Biotechnology)

Journal: Oncogene

Article Title: The epigenetic landscape of brain metastasis

doi: 10.1038/s41388-025-03315-1

Figure Lengend Snippet: This figure highlights the role of key epigenetic regulators that are frequently mutated in BrM. The data presented are derived from the MSK-MET Tropism Clinical Sequencing Cohort [ , ], which includes 300 BrM from common primary tumor sources, with a focus on breast (BR), lung (LN), and melanoma (MEL). The data were analyzed using cBioPortal to identify frequently altered epigenetic factors across these tumor types. The figure indicates the mutation rates of these epigenetic regulators for each individual source of BrM. Red colored text indicates epigenetic factors enriched in BrM compared to primary tumors. Asterisks (*) denote statistical significance ( p < 0.05) after a two-sided Fisher’s Exact test with Benjamini-Hochberg correction. The diagram also depicts chromatin in both its open and closed states with various key regulators involved. These regulators modulate chromatin accessibility and gene expression by adding, removing, or reading histone marks and DNA methylation patterns. This figure underscores the critical role of epigenetic dysregulation in the pathogenesis of brain metastasis and highlights the potential for targeting these alterations in therapeutic strategies.

Article Snippet: DNA methylation , 450 K methylation array, Illumina , Fresh frozen patient breast cancer brain metastasis tumor samples ( n = 30) , Brain metastatic breast cancer , N/A (data in Supplementary Materials of the paper) , Pangeni et al. [ ] .

Techniques: Derivative Assay, Sequencing, Mutagenesis, Gene Expression, DNA Methylation Assay

Journal: Oncogene

Article Title: The epigenetic landscape of brain metastasis

doi: 10.1038/s41388-025-03315-1

Figure Lengend Snippet: Brain metastasis is the result of a highly complex series of events, all of which are subject to epigenetic control. Any imbalance in these epigenetic mechanisms can promote brain metastatic processes. CSCs, which initiate metastatic homing, can be driven by the upregulation of genes in the Notch and Hippo pathways through the SWI/SNF complex. Primary tumor-derived EVs, influenced by RNA demethylase FTO , can prime the brain metastatic niche. Contents of these EVs, such as miR-181c, can facilitate degradation of the BBB by downregulating PDPK1 in endothelial cells, allowing metastatic cells to pass into the brain. Once in the brain, metastatic cells interact with their microenvironmental niche. Resident astrocytes can promote cancer cell dormancy by triggering DNMT1 downregulation, which increases the expression of L1CAM and CRYAB while downregulating Wnt signaling. Metastatic cells and reactive glial cells induce transcriptional reprogramming of astrocytes, promoting a more immunosuppressive, pro-tumorigenic microenvironment through the production of IL-10, IFN-α , and BDNF . These pro-tumorigenic astrocytes can further support cancer cell growth through direct junctions with cancer cells, such as connexin 43, leading to the upregulation of MYC and TGLI1 , or through astrocyte-secreted molecules like miR-19a, which triggers PTEN loss in cancer cells. Supported by all aspects of the brain microenvironment, metastatic cancer cells can proliferate uncontrollably to form metastases, a process further promoted by epigenetic modulators, EZH2 and HDAC2 . Abbreviations: SWI/SNF switch/sucrose non-fermentable, EVs extracellular vesicles, FTO fat mass and obesity-associated protein (RNA demethylase), miR microRNA, PDPK1 3-phosphoinositide-dependent protein kinase-1, DNMT1 DNA methyltransferase 1, L1CAM L1 cell adhesion molecule, CRYAB crystallin alpha B, IL-10 interleukin-10, IFN-α interferon-alpha, BDNF brain-derived neurotrophic factor, EZH2 enhancer of zeste homolog 2, HDAC2 histone deacetylase 2, PTEN phosphatase and tensin homolog.

Article Snippet: DNA methylation , 450 K methylation array, Illumina , Fresh frozen patient breast cancer brain metastasis tumor samples ( n = 30) , Brain metastatic breast cancer , N/A (data in Supplementary Materials of the paper) , Pangeni et al. [ ] .

Techniques: Control, Derivative Assay, Expressing, Histone Deacetylase Assay