151 Using genomics to search for new viral causes and treatments for human cancer

Although animal polyomaviruses, such as SV40, have been critical models in cancer research for over one-half century, polyomaviruses have not—until recently—been linked to human cancer. Using digital transcriptome subtraction, Merkel cell polyomavirus (MCV) was discovered in 2008 to infect most Merkel cell carcinomas, the most severe form of skin cancer. Normally, MCV is an common and asymptomatic infection of the human skin. In Merkel cell tumors, however, the virus integrates and undergoes mutations that eliminate viral replication but allow continued expression of viral oncogenes. MCV and MCC reveal a new model for carcinogenesis in which a rare combination of xenomutations to healthy skin flora initiate a deadly cancer. Using new sequencing technologies, the causes previously-unsuspected viral cancers can be uncovered and clues for new rational drug therapies can be designed.