Mutational Landscape of Virus- and UV-Associated Merkel Cell Carcinoma Cell Lines Is Comparable to Tumor Tissue

摘要

Merkel cell carcinoma (MCC) is an aggressive, rare skin cancer which is caused either by a virus or chronic UV exposure. For both forms, distinct genetic alterations have been described; however, these observations were mostly made in tumor tissue. Since cancer cell lines are frequently used as preclinical models to investigate biological function, we considered it necessary to establish the genomic landscape of MCC cell lines by whole-exome sequencing. We confirmed the presence of UV-induced DNA damage, a high number of mutations and several coding mutations in virus-negative cell lines which were absent in virus-positive cell lines; these, however, harbored characteristic copy number variations, suggesting some virally caused genetic instability. Knowing the genomic features of MCC cell lines validates previous, and facilitates upcoming, experimental studies to discover their biological and translational relevance.