Abstract
Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Based on animal studies, a viral etiology of osteosarcoma was proposed more than a half-century ago, but no viral association with human osteosarcoma has been found. The Uyghur ethnic population in Xinjiang, China, has an unusually high prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in Uyghur osteosarcoma patients versus the general Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-activated signaling pathways important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma, and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.