Fusion of the EWSRI and ATFI genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma

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 EWSRI-ATFI 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 EWSRI-ATFI chimera represents a fusion gene that can be associated with different tumor types. Simultaneous expression of the EWSRI-ATFI and MITF-M transcripts in CCS has led to the proposal that the MITF-M promoter is transactivated by EWSRI-ATFI. 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 EWSRI-ATFI fusion protein. Activation of the EWSRI-ATFI 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. (c) 2005 Wiley-Liss, Inc.