Abstract:
Cancer is a multifaceted genetic disease characterized by the acquisition of several essential hallmarks. Notably, certain cancers exhibit horizontal transmissibility, observed across mammalian species and diverse bivalves, the latter referred to as hemic neoplasia. Within this complex landscape, epigenetic mechanisms such as histone modifications and cytosine methylation emerge as fundamental contributors to the pathogenesis of these transmissible cancers. Our study delves into the epigenetic landscape of Cerastoderma edule, focusing on whole-genome methylation and hydroxymethylation profiles in heathy specimens and transmissible neoplasias by means of Nanopore long-read sequencing. Our results unveiled a global hypomethylation in the neoplastic specimens compared to their healthy counterparts, emphasizing the role of DNA methylation in these tumorigenic processes. Furthermore, we verified that intragenic CpG methylation positively correlated with gene expression, emphasizing its role in modulating transcription in healthy and neoplastic cockles, as also highlighted by some up-methylated oncogenic genes. Hydroxymethylation levels were significantly more elevated in the neoplastic samples, particularly within satellites and complex repeats, likely related to structural functions. Additionally, our analysis also revealed distinct methylation and activity patterns in retrotransposons, providing additional insights into bivalve neoplastic processes. Altogether, these findings contribute to understanding the epigenetic dynamics of bivalve neoplasias and shed light on the roles of DNA methylation and hydroxymethylation in tumorigenesis. Understanding these epigenetic alterations holds promise for advancing our broader understanding of cancer epigenetics.
摘要:
癌症是一种多方面的遗传疾病,其特征是获得了几个基本标志。值得注意的是,某些癌症表现出水平传播性,在哺乳动物物种和不同的双壳类动物中观察到,后者被称为血肿。在这个复杂的景观中,表观遗传机制如组蛋白修饰和胞嘧啶甲基化是这些传染性癌症发病机理的基本贡献者。我们的研究探讨了头孢皮霉的表观遗传景观,通过Nanopore长读数测序,重点关注健康标本和传染性肿瘤中的全基因组甲基化和羟甲基化谱。我们的结果揭示了肿瘤标本与健康标本相比的全球低甲基化,强调DNA甲基化在这些致瘤过程中的作用。此外,我们证实基因内CpG甲基化与基因表达呈正相关,强调其在调节健康和肿瘤鸟笼转录中的作用,一些高甲基化的致癌基因也突出了这一点。在肿瘤样本中,羟甲基化水平显著升高,特别是在卫星和复杂的重复中,可能与结构功能有关。此外,我们的分析还揭示了反转录转座子中不同的甲基化和活性模式,提供对双壳类动物肿瘤过程的更多见解。总之,这些发现有助于理解双壳类肿瘤的表观遗传学动力学,并阐明DNA甲基化和羟甲基化在肿瘤发生中的作用。了解这些表观遗传学改变有望促进我们对癌症表观遗传学的更广泛理解。