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dc.contributor.authorRabidou, Kimberlie Ann Marquesen_US
dc.date.accessioned2016-06-29T18:18:48Z
dc.date.issued2016
dc.identifier.urihttps://hdl.handle.net/2144/16761
dc.description.abstractMalignant melanoma, which comprises only 2% of skin cancers cases, but is the most lethal form of skin cancer. With the prevalence of melanoma continuing to rise, there is a greater need to elucidate the mechanisms underlying disease initiation and progression. Because mutations in melanoma-associated genes account for only 10% of cases, epigenome-altering environmental factors must have a role in pathogenesis. DNA methylation and demethylation are key epigenetics processes which govern cell differentiation and development. 5-methylcytosine (5mC) is a key epigenetic mark, which undergoes oxidation to 5-hydroxymethylcytosine (5hmC), 5formylcytosine (5fC) and 5carboxycytosine (5caC) during demethylation. In melanoma, it has been established that the loss of 5hmC is a cancer hallmark and is associated with poor prognostic outcome. The roles of 5fC/5caC, however, are not known. Here, I aimed to investigate the role of 5fC/5caC in melanoma and its contribution to disease development. Using methylase-assisted bisulfite sequencing, I have mapped the genome-wide distribution of 5fC/5caC at base pair resolution in two melanoma cell lines, A2058 and Mel Juso. In both cell lines, this modification is enriched at distal regulatory elements. Comparisons of differentially methylated sites and regions between the cell lines revealed that the products of 5fC/5caC enriched genes participate in cell adhesion and cell signaling, both of which are altered during melanoma initiation and progression. Increased levels of 5fC/5caC in these genes may be a contributing factor to this deregulation. Through these studies, we aim to identify distinct regions undergoing alterations in melanoma, which can serve as diagnostic and prognostic biomarkers.en_US
dc.language.isoen_US
dc.subjectCellular biologyen_US
dc.subject5-carboxylcytosineen_US
dc.subject5-formylcytosineen_US
dc.subjectEpigeneticsen_US
dc.subjectMelanomaen_US
dc.titleGenome wide profiling of 5-formylcytosine and 5-carboxylcytosine in melanomaen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2016-06-17T00:12:53Z
dc.description.embargo2018-06-16T00:00:00Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US


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