title: EWSR1-CREB1 and EWSR1-ATF1 fusion genes in angiomatoid fibrous histiocytoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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 occurrence of a second unknown tumor-specific molecular event or, perhaps more likely, divergent differentiation programs of the putatively distinct precursor cells of AFH and clear cell sarcoma might be invoked in order to explain the two different phenotypes.
authors: Department of Pathology, Regional Hospital, Treviso, Italy.
authors: Sabrina
authors: S
authors: Rossi
authors: Kàroly
authors: K
authors: Szuhai
authors: Marije
authors: M
authors: Ijszenga
authors: Hans J
authors: HJ
authors: Tanke
authors: Lucia
authors: L
authors: Zanatta
authors: Raf
authors: R
authors: Sciot
authors: Christopher D M
authors: CD
authors: Fletcher
authors: Angelo P
authors: AP
authors: Dei Tos
authors: Pancras C W
authors: PC
authors: Hogendoorn
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D005260:Female; D051677:Histiocytoma, Malignant Fibrous / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C111598:EWS-ATF1 fusion protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors