RT Journal Article T1 Unravelling epigenetic mechanisms in Cerastoderma edule genome: a comparison of healthy and neoplastic cockles A1 Viña Feás, Alejandro A1 Temes Rodríguez, Javier A1 Vidal Capón, André A1 Novas, Samuel A1 Rodríguez Castro, Jorge A1 Pequeño Valtierra, Ana A1 Pasantes Ludeña, Juan José A1 Castro Tubío, José Manuel A1 García Souto, Daniel K1 Bivalve transmissible neoplasia K1 Epigenetics K1 Methylation K1 Cerastoderma edule K1 Transposons AB 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 PB Springer SN 1617-4615 YR 2024 FD 2024-05-25 LK http://hdl.handle.net/10347/34905 UL http://hdl.handle.net/10347/34905 LA eng NO Mol Genet Genomics 299, 58 (2024) NO This work was supported by the European Research Council (ERC) Starting Grant ‘SCUBA CANCERS’ (716290), the European Regional Development Fund (ERDF) and Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019–2022; ED431C 2020/05; ED431C 2023/28). DG-S acknowledges support from the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, under the grant ED481D-2022-001 DS Minerva RD 28 abr 2026