Biallelic Loss Mediated by Drives Angiosarcoma.

Angiosarcoma is an aggressive vascular sarcoma with an extremely poor prognosis. Because of the relative rarity of this disease, its molecular drivers and optimal treatment strategies are obscure. DICER1 is an RNase III endoribonuclease central to miRNA biogenesis, and germline mutations result in a cancer predisposition syndrome, associated with an increased risk of many tumor types. Here, we show that biallelic deletion with drives aggressive and metastatic angiosarcoma independent of other genetically engineered oncogenes or tumor suppressor loss. Angiosarcomas in mice histologically and genetically resemble human angiosarcoma. miR-23 target genes, including the oncogenes as well as , and that promote invasiveness and metastasis, were enriched in mouse and human angiosarcoma. These studies illustrate that Dicer1 can function as a traditional loss-of-function tumor suppressor gene, and they provide a fully penetrant animal model for the study of angiosarcoma development and metastasis. .