Melanoma is the deadliest form of skin cancer. In the early stages of the disease, melanoma can be treated successfully with surgery, but after metastasis survival rates drop significantly. Therefore, early and correct diagnosis is key to providing a patient with the best possible prognosis. Melanoma misdiagnosis is the second leading cause for medical malpractice claims, as an early misdiagnosis can significantly reduce a patient’s chances of survival. Thus, new biomarkers and drug targets are needed to improve the accuracy of melanoma diagnosis and treatment. Using mass spectrometry, two histone epigenetic marks that are dysregulated in melanoma were identified, histone H4 lysine 20 monomethylation (H4K20me) and histone H3 lysine 27 trimethylation (H3K27me3). This study explores H4K20me as a potential biomarker for melanoma diagnosis, and H4K20me-associated pathways as potential targets for melanoma drug development. Immunohistochemistry was performed against H3K27me3 and H4K20me to ascertain whether these histone post translational modifications (PTMs) could be used to distinguish different stages of melanoma. H3K27me3 and H4K20me were found to display differential expression patterns that can individually be used to distinguish benign nevi from melanoma; however, when considered together the diagnostic utility of these PTMs increased significantly. The work presented supports the use of combination immunohistochemistry of histone PTMs as a way to increase accuracy and confidence in the diagnosis of melanoma.
|Commitee:||Chambers, Timothy, Raney, Kevin, Shalin, Sara, Wahls, Wayne|
|School:||University of Arkansas for Medical Sciences|
|Department:||Biochemistry and Molecular Biology|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 81/1(E), Dissertation Abstracts International|
|Subjects:||Biochemistry, Molecular biology, Biology|
|Keywords:||Cancer biology, Epigenetics, H4K20me, Histone PTMs, Melanoma diagnosis, Therapeutic development|
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