EWSR1-CREB1 and EWSR1-ATF1 Fusion Genes in Angiomatoid Fibrous Histiocytoma

作者：Sabrina Rossi, Károly Szuhai, Marije IJszenga, Hans J. Tanke, Lucia Zanatta, Raf Sciot, Christopher D.�M. Fletcher, Angelo Paolo Dei Tos, Pancras C.W. Hogendoorn · 发表于：Clinical Cancer Research · 年份：2007 · DOI：10.1158/1078-0432.ccr-07-1744 · 被引用次数：233 · 研究领域：Sarcoma Diagnosis and Treatment、Vascular Tumors and Angiosarcomas、Cardiac tumors and thrombi

PURPOSE: Angiomatoid fibrous histiocytoma (AFH) is a low-grade mesenchymal neoplasm which usually occurs in children and adolescents. Either FUS-ATF1 or EWSR1-ATF1 have been detected in the few cases published, pointing to the interchangeable role of FUS and EWSR1 in this entity. EWSR1-ATF1 also represents the most frequent genetic alteration in clear cell sarcoma, suggesting the existence of a molecular homology between these two histotypes. We investigated the presence of EWSR1-CREB1, recently found in gastrointestinal clear cell sarcoma, and FUS-CREB1, as well as the already reported FUS-ATF1 and EWSR1-ATF1 in a series of AFH. EXPERIMENTAL DESIGN: Fourteen cases were analyzed by fluorescence in situ hybridization (FISH) on paraffin-embedded tissue sections, using a commercial EWSR1 probe and custom-designed probes for FUS, ATF1, and CREB1. In two cases, four-color FISH was also done. Reverse transcription-PCR for the four hypothetical fusion genes was done in one case, for which frozen material was available. RESULTS: Thirteen cases showed rearrangements of both EWSR1 and CREB1, whereas one case showed the rearrangement of both EWSR1 and ATF1. Four-color FISH confirmed the results in two selected cases. Reverse transcription-PCR showed EWSR1-CREB1 transcript in the case analyzed. CONCLUSION: We identified the presence of either EWSR1-CREB1 or EWSR1-ATF1 in all the cases, strengthening the concept of chromosomal promiscuity between AFH and clear cell sarcoma. Either the occ...