Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma

Genes Chromosomes Cancer. 2005 Sep;44(1):97-102. doi: 10.1002/gcc.20201.


Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that usually occurs in children and young adults. Only two cases of AFH with genetic rearrangements have been reported previously; both of these had a FUS-ATF1 fusion gene. We have studied an AFH from a 9-year-old boy whose tumor displayed a t(12;22)(q13;q12) as the sole cytogenetic aberration. FISH,RT-PCR, and sequence analyses revealed an EWSR1-ATF1 fusion gene that has previously been reported in clear cell sarcoma (CCS), a soft tissue sarcoma that is morphologically and clinically distinct from AFH. This study thus has demonstrated that the EWSR1-ATF1 chimera represents a fusion gene that can be associated with different tumor types. Simultaneous expression of the EWSR1-ATF1 and MITF-M transcripts in CCS has led to the proposal that the MITF-M promoter is transactivated by EWSR1-ATF1. The AFH, however, did not express the MITF-M transcript, supporting the theory that MITF-M expression in CCS is a reflection of its cellular origin, rather than a consequence of the presence of an EWSR1-ATF1 fusion protein. Activation of the EWSR1-ATF1 oncogene is probably an early step in the transformation process, but the overall gene expression patterns are likely to vary considerably between AFH and CCS, in keeping with their clinicopathologic differences.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1
  • Adenocarcinoma, Clear Cell / genetics
  • Artificial Gene Fusion*
  • Base Sequence
  • Calmodulin-Binding Proteins / genetics*
  • Child
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 22
  • DNA Primers
  • DNA-Binding Proteins / genetics*
  • Histiocytoma, Benign Fibrous / genetics*
  • Histiocytoma, Benign Fibrous / pathology
  • Humans
  • Karyotyping
  • Male
  • Microphthalmia-Associated Transcription Factor
  • Nuclear Proteins / genetics*
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / genetics*
  • Regulatory Factor X Transcription Factors
  • Sequence Deletion
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Translocation, Genetic


  • ATF1 protein, human
  • Activating Transcription Factor 1
  • Calmodulin-Binding Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • EWSR1 protein, human
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Nuclear Proteins
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors