Diagnosis of known sarcoma fusions and novel fusion partners by targeted RNA sequencing with identification of a recurrent ACTB-FOSB fusion in pseudomyogenic hemangioendothelioma.
Recurrent SERPINE1-FOSB gene fusions have been reported as the hallmark genetic abnormality in PHE, however, in our experience, a number of cases with typical histology lack this genetic abnormality.
Interestingly, in FOSB overexpressing cells, telatinib specifically affected PDGFRA, FLT1, and FLT4 signaling and downregulated SERPINE1, thereby affecting the self-regulation of the fusion gene.<b>Conclusions:</b> We provide a biological substantiation of a complete clinical remission that was seen in a patient with PHE, showing that telatinib indirectly interferes with the self-regulated expression of the fusion product.
We previously identified characteristic FOSB expression in pseudomyogenic hemangioendothelioma (PHE) with a specific SERPINE1-FOSB fusion, revealing the usefulness of FOSB immunohistochemistry in the differential diagnosis of PHE and its mimics.
Although FOSB-rearranged EH do not show significant morphologic overlap with SERPINE1-FOSB fusion-positive pseudomyogenic hemangioendothelioma, FOSB oncogenic activation is emerging as an important event in these benign and intermediate groups of vascular tumors.