"Merkel cell carcinoma and a new polyomavirus"
Merkel cell carcinoma (MCC) is a deadly neuroendocrine skin cancer that is diagnosed in over 1,500 individuals each year in the United States and causes 500 deaths. MCC has long been linked to sun exposure, advanced age, and interestingly immune suppression. Recently, a new polyomavirus, the Merkel cell polyomavirus (MCPyV), was found to be associated with Merkel cell carcinoma. This virus has several features that suggest it may play a role in MCC carcinogenesis but remains to be functionally characterized.
Interestingly, not all MCC tumors have detectable MCPyV. This immediately suggests two potential groups of MCC, which may have different disease courses or responsiveness to therapies. Using a remarkable repository of annotated MCC tumors, I will test whether patients with MCPyV negative and positive tumors have differences in disease-specific survival or response to therapy.
To investigate a possible functional role of MCPyV in MCC tumor development, I will stably express virally encoded genes in primary fibroblasts and keratinocytes and assess their performance on standard cell-culture assays of transformation.
Finally, there is a great need for new Merkel cell carcinoma cell lines, as only approximately 20 such lines exist of which only a few grow well. In particular, there are no reported MCPyV positive MCC cell lines. To address this, we will attempt to grow new MCC cell lines from leftover surgical specimens.
This interdisciplinary proposal combines the complementary resources of two expert laboratories. In the Nghiem Lab, a MCC-focused translational lab, I will benefit from a large repository of clinically annotated MCC tumor tissues and 10 years of MCC expertise. In the Galloway Lab, a molecular virology lab, I will profit from their extensive knowledge of DNA tumor viruses and experience in cell line creation and assays of tumorigenesis.