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https://hdl.handle.net/20.500.12202/1592
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DC Field | Value | Language |
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dc.contributor.author | Wijetunga, Neil Ari | |
dc.date.accessioned | 2018-07-12T17:42:36Z | |
dc.date.available | 2018-07-12T17:42:36Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Source: Dissertation Abstracts International, Volume: 77-05(E), Section: B.;Advisors: John Greally. | |
dc.identifier.uri | https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3664679 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12202/1592 | |
dc.description.abstract | It is estimated that chronic infections account for 2 million cancers worldwide every year. As much as 30% of the population in developing countries has a chronic infection associated with cancer. Specifically, infection with Human Papilloma (HPV) and Hepatitis C (HCV) viruses account for the majority of infection-related cancers. Because oncogenic viruses often lead to cancer decades after the initial infection, it is possible that they introduce a "field defect" through altered epigenetic states that predisposes multiple cells to tumorogenesis. Therefore, I hypothesized that viral modification of the host epigenome after chronic infection can predispose to a precancerous state. By characterizing the epigenome in non-disease states and disease states, including preneoplastic lesions and tumors associated with oncogenic virus infection, I elucidated the patterns and effects associated with these modifications.;In Chapter 1, I review the progression between normal cells and cancer, considering the contribution of epigenetic dysregulation to developing HCV-related and HPV-related carcinoma. In Chapter 2, I characterize the normal variability in DNA methylation in hematopoietic stem and progenitor cells, introducing the concept of the `meta-epigenome', and demonstrating that an assayed epigenome is an average of a finite number of distinct epigenomes. In Chapters 3 and 5, I describe epigenetic dysregulation in disease progression associated with HPV and HCV infection, respectively. For both studies, I find that genes that are targeted by the polycomb repressive complex 2 in stem cells are enriched for increased DNA methylation at their cis-regulatory elements. Additionally, in Chapter 4, I detail an innovative technique that I developed for integrating multilevel genomics and epigenomics research. Finally, in Chapter 6, I discuss the integrated study findings, implications of my work, and directions for further study.;In this thesis, I develop and use novel analytical approaches to demonstrate that the emergence of stem cell signatures in preneoplastic lesions is detectable before tumorigenesis and represents a future target for early clinical intervention. The emergence of a stem-like epigenetic state in a subset of cells within preneoplastic lesions provides insight into one possible mechanism for carcinogenesis. | |
dc.publisher | ProQuest Dissertations & Theses | |
dc.subject | Genetics. | |
dc.subject | Oncology. | |
dc.subject | Bioinformatics. | |
dc.title | Preneoplastic epigenomic dysregulation associated with oncogenic viral infection | |
dc.type | Dissertation | |
Appears in Collections: | Albert Einstein College of Medicine: Doctoral Dissertations |
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