Insights into determinants of cancer susceptibility, initiation, and progression:studies on medulloblastoma and Histiocytic Sarcoma in mouse models

Abstract

This dissertation presents a discussion of both perigestational dietary influence on cancer predisposition as well as somatic genetic determinants of cancer development. Both projects used genetically engineered mouse models of cancer. The introductory chapter gives a brief historical introduction to cancer, background information on models of cancer, and a short description of our current understanding of cancer. Chapter two presents data on how maternal diet can affect the risk for medulloblastoma in offspring. Medulloblastoma presents a dismal prognosis even for the patients who are successfully treated. Prevention strategies are therefore of great interest in addressing this disease. Chapter three discusses a mouse model of Histiocytic Sarcoma (HS) that was developed to identify genes that can contribute to initiation and cause progression of disease. The genetics of HS are not well understood. Our model could provide important information on molecular targets that can be used to treat this dreadful disease. The final, fourth chapter, provides a brief and broad overview of some of the major future likely sources of cancer control success with a focus on new research.