
Am J Stem Cell 2012;1(1):59-74
Review Article
Loss of imprinting of IGF2 and the epigenetic progenitor model of cancer
Mark B. Leick, Christopher J. Shoff, Erwin C. Wang, Jaclyn C. Congress, G. Ian Gallicano
Georgetown University School of Medicine, Department of Biochemistry and Molecular & Cellular Biology, Washington DC, USA.
Received August 15, 2011; accepted August 19, 2011; Epub August 19, 2011; published January 1, 2012
Abstract: Among the hypotheses discussing cancer formation, the cancer stem cell (CSC) theory is one receiving widespread support.
One version of this theory states that changes in otherwise healthy cells can cause formation of tumor-initiating cells (TICs), which have
the potential to create precancerous stem cells that can lead to CSC formation. These CSCs can be rare, in contrast to their differentiated
progeny, which give rise to the vast majority of the tumor mass in most cancers. Loss of imprinting (LOI) of the insulin-like growth factor-2
(IGF2) gene is one change that can produce these TICs via an epigenetic progenitor model of tumorigenesis. While IGF2 usually
supports normal cellular growth, LOI of IGF2 may lead to overexpression of the gene and moreover global chromatin instability. This
modification has been observed in many forms of cancer, and given the effect of LOI of IGF2 and its role in cancer, detecting a loss of
imprinting in this gene could serve as a valuable diagnostic tool. Preclinical data has shown some progress in identifying therapeutic
approaches seeking to exploit this relationship. Thus, further research surrounding LOI of IGF2 could lead to increased understanding of
several cancer types and enhance therapies against these diseases. (AJSC1108003).
Keywords: Insulin like growth factor 2 (IGF2), cancer stem cell, epigenetic, progenitor, loss of imprinting
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Address all correspondence to:
G. Ian Gallicano, PhD
Department of Biochemistry and Molecular & Cellular Biology
Georgetown University Medical Center
3900 Reservoir Rd. NW
Medical Dental Building, Room NE205
Washington, DC 20057
E-mail: gig@georgetown.edu

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