DNA methylation profiling of fish tumours

[摘要] Assessment of disease status in fish is used as an indicator of the biological effects of contaminants in the marine environment. At some UK offshore sites the prevalence of liver tumours in Limanda limanda (dab) exceeds 20%. However, the molecular mechanisms of tumour formation and the causative agents are not known. The contribution of epigenetic mechanisms, although well-established in human tumourigenesis, is under-studied in tumours of aquatic species. In this thesis, alteration in the DNA methylation patterns in tumours of two fish species, the model species zebrafish (Danio rerio) and the un-sequenced marine flatfish dab, were investigated. The data presented provided a comprehensive characterisation of DNA methylation pattern in zebrafish liver and the first evidence of alterations in DNA methylation profiles of key genes in tumourigenesis pathways in any aquatic species. A statistically significant lower level of global DNA methylation was demonstrated in hepatocellular adenoma (HCA) and non-cancerous surrounding liver tissue (ST) compared to liver of non-cancer bearing dab. The evidence presented in this thesis suggests that chronic exposure to a mixture of pollutants contribute to global DNA hypomethylation followed by further epigenetic and genomic changes, leading to the development of tumours in dab. These findings suggest a link between the environment, epigenome and cancer in fish tumours in the wild.

[发布机构] University:University of Birmingham;Department:School of Biosciences

[关键词] Q Science;QH Natural history;QH301 Biology