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Title: Pathways to Pediatric Cancer
Authors: Harjo, Alexandra Kathleen
Advisors: Tilghman, Shirley
Department: Molecular Biology
Class Year: 2013
Abstract: The past century has been a dynamic era for understanding cancer development. Childhood cancer is especially tragic and confounds common assumptions about how cancer develops. Although many biologists have proposed models of carcinogenesis, the ability of the models to explain early childhood cancers remains limited. The classic models, including Knudson’s “two-hit” hypothesis, have not been updated to incorporate new understandings of epigenetic involvement and do not sufficiently integrate cell-of-origin specificity. I have provided a review of the most prominent cancer models presented to date, and assessed the applicability of these models to common childhood cancers. Four common pediatric cancers serve as good examples of the diverse molecular origins and mechanisms involved in childhood cancer: retinoblastoma, Wilms tumor, acute lymphoblastic leukemia, and medulloblastoma. Based on an examination of these cancers, I identified three primary factors that determine the age-specificity of a cancer: the cell-of-origin, the origin cell’s molecular vulnerabilities, and the origin cell’s developmental features. The combination of rapid cell division and differentiation in a cell population increases the likelihood of genetic and epigenetic errors that can induce neoplastic transformation. The most common childhood cancers arise in pluripotent cells undergoing rapid division and differentiation.
Extent: 108 pages
Access Restrictions: Walk-in Access. This thesis can only be viewed on computer terminals at the Mudd Manuscript Library.
Type of Material: Princeton University Senior Theses
Language: en_US
Appears in Collections:Molecular Biology, 1954-2020

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