Exploring the role of polyploidy in tumor progression

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Recent genomic analysis of human cancer sequencing data estimates over one third of human tumors undergo whole-genome duplication events. While applications of sequencing technology have revealed the prevalence of polyploidy in human cancer, the functional implications of polyploidy in cancer remain poorly defined. I propose to experimentally assess the effects of polyploidy on tumor progression using a murine model of breast cancer tumorigenesis. First, I will determine how polyploidy affects primary tumor growth. I will then determine if polyploidy influences the genetic alterations selected for in primary tumors. Finally, I will assess the consequences of polyploidy with respect to disease recurrence. I hypothesize that polyploidy promotes tumor growth in the context of primary tumor formation and recurrence, while uniquely shaping the genetic alterations present in tumors. Understanding how whole-genome duplication events affect tumor progression will provide important insight into the functional implications of polyploidy in cancer, and will yield a better understanding of events that shape the cancer genome.