Cancer

Telomerase is upregulated in the vast majority of human cancers, where it serves in part to maintain telomeres, thus endowing cancers with unlimited proliferative potential. Despite the importance of telomerase upregulation late in tumor development, telomeres shorten dramatically during the early stages of tumorigenesis, and this telomere attrition can profoundly alter tumorigenesis, either impairing or enhancing the development of early neoplastic lesions depending on the genetic context. In p53-mutant backgrounds, telomere shortening leads to cycles of chromosomal fusion-bridge-breakage that can fuel cancer initiation. These cycles of instability lead to non-reciprocal translocations and changes in gene copy number, both hallmarks of chromosomal instability in human carcinomas. We seek to understand how telomere dysfunction leads to cancer initiation by creating sophisticated genetic models of cancer in mice. These models will facilitate detailed studies of cancer initiation and progression.