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Epigenetic changes found in uterine decidual and placental tissues can also be found in the breast cancer microenvironment of the same unique patient: description and potential interpretations

机译:在子宫蜕膜和胎盘组织中发现的表观遗传变化也可以在同一位独特患者的乳腺癌微环境中发现:描述和潜在解释

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摘要

Microenvironmental properties are thought to be responsible for feto-maternal tolerance. Speculatively, ectopic expression of placental gene programs might also be related to cancer cells’ ability to escape from immune vigilance mechanisms during carcinogenesis and cancer progression. Recently, we published the first human genomic evidence of similar immune related gene expression profiles in both placenta (placenta and decidual tissue) and cancer (both primary and metastatic) in the same patient with lymph-node positive breast carcinoma during pregnancy. Here we report the first epigenomic analysis of these tissue samples and describe their main findings, with respect to immune related genes regulation (over or under expressed) in cancer cells with regards placental tissues. We confirm significant similarities, and hierarchical clustering (both unsupervised and supervised), in CpG island methylation patterns between decidual/placental and cancer microenvironments, which cannot be easily explained by simple models or unique pathways. Several different cell types are probably involved in these complex immune regulation mechanisms. Cancers may somehow “hijack” gene programs evolved over millions of years to allow for feto-maternal tolerance in placental mammals in order to escape from immune vigilance and spread locally or to distant sites.
机译:认为微环境特性是胎儿-母亲耐受性的原因。从推测上讲,胎盘基因程序的异位表达也可能与癌细胞在癌变和癌症发展过程中逃避免疫警惕机制的能力有关。最近,我们在妊娠期间同一淋巴结阳性乳腺癌患者的胎盘(胎盘和蜕膜组织)和癌症(原发性和转移性)中首次发表了类似的免疫相关基因表达谱的人类基因组学证据。在这里,我们报告了这些组织样品的首次表观基因组学分析,并描述了它们的主要发现,涉及胎盘组织中癌细胞中免疫相关基因的调控(表达过度或表达不足)。我们在蜕膜/胎盘和癌症微环境之间的CpG岛甲基化模式中证实了显着的相似性和分层聚类(无监督和有监督),这不能用简单的模型或独特的途径轻易解释。这些复杂的免疫调节机制可能涉及几种不同的细胞类型。癌症可能以某种方式进化了数百万年的“劫持”基因程序,以允许胎盘哺乳动物耐受母婴,从而逃避了免疫警惕并在本地或远处扩散。

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