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On the origins of cancer cell identity : epigenetic deregulation of cellular states / by Kevin Johnson

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Author	Johnson, Kevin C.
Title	On the origins of cancer cell identity : epigenetic deregulation of cellular states / by Kevin Johnson
Date	2016
Abstract	The identification of molecular alterations present in cancer is critical to better understand carcinogenesis as well as the clinical trajectories of patients with malignant tumors. Early detection and application of appropriate treatment strategies are major factors in the successful treatment of cancer. However, the relationship between cancer risk factors and the molecular alterations that initiate and promote carcinogenesis remain unclear. To this end, the research presented herein uses interdisciplinary techniques from molecular biology, epidemiology, and statistical genomics. Cytosine modifications were measured genome-wide across the spectrum of cancer from disease-free normal breast tissue, preinvasive breast lesions, invasive breast cancer, and primary brain tumors. We identified shifts in DNA methylation patterns that were associated with known breast cancer risk factors in non-diseased tissues as well as alterations that distinguished patients with pre-invasive breast tumors at the greatest risk of developing invasive cancer. We demonstrated that the aggregate impact of epigenetic dysregulation in invasive breast cancer is associated with tumor phenotype. Finally, we discovered that 5-hydroxymethylcytosine localizes to enhancer elements and is associated with patient survival in glioblastoma. Broadly, this research provides evidence from population-based studies of epigenetic differences and provides rationale for future studies to investigate the functional roles of epigenetic alterations in cancer.
Description	1 online resource (x, 228 leaves) : illustrations (mostly color)
Format	application/pdf
College	Geisel School of Medicine at Dartmouth -- Experimental and Molecular Medicine Program.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D)--Dartmouth College.
Copyright	Made available by the author under a Creative Commons Attribution-NonCommercial License.; Made available by the Trustees of Dartmouth College under a Creative Commons Attribution-NonCommercial License. https://creativecommons.org/licenses/by-nc/4.0/
DOI	https://doi.org/10.1349/ddlp.2160

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On the origins of cancer cell identity : epigenetic deregulation of cellular states / by Kevin Johnson

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