Our understanding of the key molecular and cellular changes that cause cancer initiation and progression are still lacking, with only a few studies that have comprehensively profiled the genomic alterations found in pre-cancerous and normal tissues. As a result, little knowledge exist regarding which lesions will progress into cancer, and which will regress or remain stable. Characterization of these early molecular alterations is instrumental to the development of biomarkers for early detection, and for suggesting preventive interventions to reverse or delay the development of cancer. In this project we focus on characterizing the genetic alterations and environmental changes occurring in pre-cancerous and normal tissues, trying to identify the molecular features that distinguish between normal clonal expansions and those with higher likelihood of becoming cancer.