Evaluating the Role of ACTL6A and ACTL6B in the Pathogenesis of Polyomavirus Driven Merkel Cell Carcinoma

Abstract

Merkel Cell Carcinoma (MCC) is a rare (0.2 - 0.45 cases per 100,000) but extremely aggressive form of dermal neoplasm with a very poor prognosis. Approximately 53% MCCs occur in the head and neck, while 35% occur in the extremities. MCC is highly metastatic - about 75% to 83% patients develop metastases. The carcinoma commonly spreads to the lymph nodes first, and eventually metastasizes to the brain, bones, liver or lungs. The nonspecific characteristics of MCC make exact diagnosis extremely difficult. Most diagnoses occur only in very late stages, upon performance of a biopsy. Merkel Cells are thought to be involved in mechanoreception and sensory perception. The exact origin of Merkel Cells is still controversial and unknown. It is thought that it might have an epidermal stem cell origin or a neural crest origin. Similarly, while it is known that old age, long-term exposure to sun, as well as a weak immune system greatly increase the risk of MCC, the exact causes of this neoplasm are unknown. The Merkel Cell Polyomavirus (MCPyV) is found in a significantly large percentage of MCCs. However, since this virus is relatively common and MCC extremely rare, the exact role of the virus in the pathogenesis of MCC is still unknown. Recent research has identified possible roles of various proteins and their interaction with MCPyV in the transformation of Merkel Cells. One such protein –Actin like 6A (ACTL6A) – is known to bestow stem cell like properties to various cells and has a role in many cancers. The goal of my research is to focus on this protein, as well on its highly related but distinct homolog, Actin like 6B (ACTL6B), and evaluate their role in MCC. The research specifically looks at the levels of ACTL6A and ACTL6B in MCC and compares cell viability and apoptosis levels between ACTL6A positive versus ACTL6A knockout MCC cells.