Abstract SY15-01: Merkel cell polyomavirus: its role in pathogenesis and its potential as a molecular target.

Abstract

Abstract Merkel cell carcinoma (MCC) was first described as a pathologic entity in 1972, and is an uncommon but aggressive skin cancer with a high propensity for metastasis and recurrence. In 2008, a new human polyomavirus, Merkel cell polyomavirus (MCV) was discovered by digital transcriptome subtraction in an MCC lesion and is now one of eight new human polyomaviruses described in the past five years. MCV is part of the normal, healthy skin flora but causes cancer after viral genome mutations eliminate its replication capacity. Further, MCV is clonally integrated in 70-80% of MCC tumors suggesting a primary role for its involvement in MCV infected MCCs. The MCV genome is ~5400bp and has features including early, late, and non-coding regulatory regions conserved with other polyomaviruses. The MCV early region encodes for two potential viral oncoproteins: large T antigen (LT) and small T antigen (ST). Experiments show these proteins are expressed in MCC tumor cells from patient biopsies, and that MCV-positive MCC cell lines undergo growth arrest and/or cell death upon T antigen knockdown by short hairpin RNA (shRNA). These experiments provide direct experimental evidence that T antigen expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC. While similar to known polyomaviruses, MCV oncogenes act in new ways, such as activation of the survivin oncoprotein and PP2A-independent targeting of cap-dependent translation. In five years, the diagnosis and treatment potential for an intractable and enigmatic cancer has dramatically changed through the discovery of a viral cause of MCC. Citation Format: Yuan Chang. Merkel cell polyomavirus: its role in pathogenesis and its potential as a molecular target. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY15-01. doi:10.1158/1538-7445.AM2013-SY15-01