Ewsr1-Creb1 Is The Predominant Gene Fusion In Angiomatoid Fibrous Histiocytoma

The molecular hallmark of angionnatoid fibrous histiocytoma (AFH) is not well defined, with only six cases with specific gene fusions reported to date, consisting of either FUS-ATFI or EWSRI-ATFI. To address this, we investigated the presence of FUS-ATFI, EWSRI-ATFI, and the highly related EWSRI-CREBI fusion in a group of nine AFHs. All cases were subjected to RT-PCR for EWSRI-ATFI and EWSRI-CREBI. FISH for EWSRI and FUS rearrangements was performed in most cases. Transcriptional profiling was performed in three tumors and their gene expression was compared to five clear cell sarcomas expressing either the EWSRI-ATFI or EWSRI-CREBI fusion. By RT-PCR, eight out of nine tumors showed the presence of the EWSRI-CREBI fusion, while one had an EWSRI-ATFI transcript. FISH showed evidence of EWSRI rearrangement in seven out of eight cases. Karyotypic analysis performed in one tumor showed a t(2;22)(q33;q12). High transcript levels were noted for TFE3 in AFH tumors, while overexpression of genes involved in melanogenesis, such as MITF GP100, and MET was noted in somatic clear cell sarcomas. We report for the first time the presence of EWSRI-CREBI in AFH, which now appears to be the most frequent gene fusion in this tumor. EWSR/-CREBI is a novel translocation recently described in clear cell sarcoma of the GI tract. EWSRI-ATFI, identified in some AFH cases, is the most common genetic abnormality in soft tissue clear cell sarcoma. Thus, identical fusions involving ATFI and CREBI are found in two distinct sarcomas, which may be able to transform two different types of mesenchymal precursor cells, unlike most other sarcoma gene fusions. (c) 2007 Wiley-Liss, Inc.