To identify genetic alterations present in Merkel cell carcinoma, we have conducted molecular analyses of human tumors and cancer cell lines across multiple genome-wide platforms to assay gene expression, identify gene mutations, and characterize chromosomal alterations. These data are being analyzed to identify key driver alterations for this tumor. We are also generating mice where oncogenic modifications are carried out in specific skin lineages in an attempt to transform Merkel cells in vivo. In addition, we are developing and characterizing cancer cell lines of Merkel cell carcinoma for in vitro and xenograft studies. We are also developing clinical biomarkers for Merkel cell carcinoma. Finally we are conducting high throughput small molecule and genetic knockdown screens to identify pathways important for tumor survival and identify novel treatments for Merkel cell carcinoma.