Electronic Thesis/Dissertation


Development of Cancer-Specific DNA Methylation Biomarkers Open Access

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One in four deaths in the United States is due to cancer, despite an emphasis on prevention, early detection, and treatment that has lowered cancer death rates by 20% in the past two decades. Advances in screening, prevention, and treatment have the potential to change cancer incidence and reduce the cost of treating cancer. Many researchers in academia, industry, and government have designed large-scale systematic research pipelines for biomarker discovery. Interestingly, despite advancements, we see that the number of biomarkers receiving Food and Drug Administration (FDA) clearance has declined substantially over the last 10 years. Overwhelmingly, biomarkers identified in the literature face an uphill battle to be used in clinical settings as they suffer from many factors that can cause failure. In this research, I identify and investigate a novel class of differentially methylated loci that have potential as pan-cancer biomarkers, including within ZNF154, TLX1, GALR1, and SEPT9 gene bodies. I describe a systematic approach from identification to classification with emphasis on validation through high-throughput high-resolution methods of methylation analysis across multiple cancer types and subtypes in both solid tissue and blood plasma samples. This establishes a basis to assess signal strength and its clinical utility towards a minimally invasive blood-based diagnostic test.

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