Field cancerization is a condition of major clinical significance consisting of widespread tissue alterations associated with multiple and recurrent primary tumors. Activation of stromal fibroblasts into cancer associated fibroblasts (CAFs) is most frequently viewed as secondary to changes in the epithelium. However, our previous work indicated that it can play a primary role in epithelial cancer development. We are currently exploring a multistep process of CAF activation and expansion based on a combination of genetic and/or epigenetic events. Whether or not chromosomal changes of functional significance occur in this context remain to be established. In our future work, we will address this question focusing on the role of a specific DNA- binding protein, CSL, in control of chromosome stability and telomere maintenance. CSL expression and function are commonly compromised in CAFs and we will test whether, as a result, these cells acquire specific chromosomal alterations that confer a growth advantage important for cancer stromal cell expansion.