Christopher Spock

A Common Polymorphism within the IGF2 Imprinting Control Region Is Associated with Parent of Origin Specific Effects in Infantile Hemangiomas

Infantile hemangioma (IH) is the most common tumor of the pediatric age group, affecting up to 4% of newborns ranging from inconsequential blemishes, to highly aggressive tumors. Following well defined growth phases (proliferative, plateau involutional) IH usually regress into a fibro-fatty residuum. Despite the high prevalence of IH, little is known regarding the pathogenesis of disease. A reported six fold decrease in IGF2 expression (correlating with transformation of proliferative to involuted lesions) prompted us to study the IGF-2 axis further. We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor. IGF2 expression was strongly and positively related to BORIS transcript expression. Furthermore, a stronger association was made when comparing BORIS levels against the expression of CTCF via either a percentage or difference between the two. A common C/T polymorphism at CTCF BS6 appeared to modify the correlation between CTCF/BORIS and IGF2 expression in a parent of origin specific manner. Moreover, these effects may have phenotypic consequences as tumor growth also correlates with the genotype at CTCF BS6. This may provide a framework for explaining the clinical variability seen in IH and suggests new insights regarding CTCF and BORIS related functionality in both normal and malignant states.

An Itchy Mouse: A Potential Model of Atopic Dermatitis

For answers, visit our website or scan the adjacent tag. Atopic dermatitis (AD) is a common chronic inflammatory skin disorder with both acute and chronic stages (Akdis et al., 2006). Often referred to as “the itch that scratches,” AD is characterized by severe pruritus, which may substantially impact the quality of life in sufferers. Recently, human protease-activated receptor-2 (PAR-2) was found to mediate itch (Reddy et al., 2010), generating considerable interest in compounds that activate this receptor. Among these compounds is cathepsin S (CTSS), a lysosomal cysteine protease that functions in a variety of ways, including as an elastase in alveolar macrophages. This compound may also play a role in the degradation of antigenic proteins into peptides for presentation on major histocompatibility complex class II molecules. To study the role of CTSS, Kim et al. (2012, this issue) utilized a transgenic mouse that overexpresses human CTSS. The investigators hypothesized that over expression of human CTSS in this model would lead to the AD-like symptoms and signs of itching and scratching and histopathological changes that resemble those in AD. Indeed, the transgenic mice that overexpressed CTSS scratched more, and this increased scratching led to reddening, scaling, and thickening of the skin. PAR-2 expression was also increased as a result of CTSS overexpression, and both CTSS and PAR-2 levels correlated with a thickened epidermis. Although barrier function was not examined, a variety of cytokines, including IL-4, IL-10, tumor necrosis factor-a, IL-2, IFN-g, IL-1b, monocyte chemotactic protein-1, and granulocyte–macrophage colony-stimulating factor, were analyzed. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to the supplementary information online .