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Epigenetic field defects in progression to cancer
Authors:Carol Bernstein  Valentine Nfonsam  Anil Ramarao Prasad  Harris Bernstein
Affiliation:Carol Bernstein, Harris Bernstein, Department of Cellular and Molecular Medicine, College of Medicine, University of Arizona, Tucson, AZ 85724, United StatesValentine Nfonsam, Department of Surgery, College of Medicine, University of Arizona, Tucson, AZ 85724, United StatesAnil Ramarao Prasad, Department of Pathology, College of Medicine, University of Arizona, Tucson, AZ 85724, United States
Abstract:
A field defect is a field of pre-malignant tissue in which a new cancer is likely to arise. Field defects often appear to be histologically normal under the microscope. Recent research indicates that cells within a field defect characteristically have an increased frequency of epigenetic alterations and these may be fundamentally important as underlying factors in progression to cancer. However, understanding of epigenetic field defects is at an early stage, and the work of Katsurano et al published this year, is a key contribution to this field. One question examined by Katsurano et al was how early could the formation of an epigenetic field defect be detected in a mouse colitis model of tumorigenesis. They highlighted a number of measurable epigenetic alterations, detected very early in normal appearing tissue undergoing histologically invisible tumorigenesis. They also documented the increasing presence of the epigenetic alterations at successive times during progression to cancer. In this commentary, we offer a perspective on the changes they observed within a broader sequence of epigenetic events that occur in progression to cancer. In particular, we highlight the likely central role of epigenetic deficiencies in DNA repair gene expression that arise during progression to cancer.
Keywords:Field defect   Epigenetics   Tumorigenesis   Carcinogenesis   DNA damage   DNA repair   Colon cancer   Mouse   Human
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