We here show that a t(7;16)(q33;p11) in two cases of low grade fibromyxoid sarcoma fuses the FUS gene to BBF2H7, a previously uncharacterized gene that is homologous to the Drosophila Bbf-2 gene.
The results indicated that FUS/CREB3L2 is specifically associated with LGFMS and that RT-PCR or FISH analysis may be useful for the differential diagnosis.
Reverse transcriptase-polymerase chain reaction analysis disclosed a FUS/CREB3L2 fusion transcript in 22 of the 23 (96%) cases that remained classified as LGFMS after the histologic re-evaluation and from which RNA of sufficient quality could be extracted, whereas none of the cases that were classified as other tumor types was fusion-positive.
We also tested a primer set to detect the FUS-CREB3L1 fusion transcript, which is a rare variant of the gene fusion in LGFMS, although no PCR products were identified in any case.
Reported herein is a case of primary pulmonary HSCT that had FUS-CREB3L2 fusion transcripts, a product of characteristic chromosomal abnormality t(7;16)(q33;p11) of HSCT and LGFMS.
To that end, dual-color, break-apart fluorescence in situ hybridization (FISH) probes spanning the genomic regions of EWSR1 (22q12), DDIT3 (12q13), and FUS (16p11) (Vysis, Downer's Grove, IL) were evaluated in formalin-fixed, paraffin-embedded tissues from myxoid neoplasms, including intramuscular myxoma (n=10), myxoid liposarcoma (n=18), low-grade fibromyxoid sarcoma (n=10), extraskeletal myxoid chondrosarcoma (n=13), and myxofibrosarcoma (n=8).
Postoperative pathology of the resected specimen revealed the tumor to be LGFMS based on its histological appearance, immunohistological staining, and evidence of fused in sarcoma (FUS) translocation by fluorescence in situ hybridization.
RT-PCR and FISH for the FUS-CREB3L2 fusion transcript are useful tools for confirming LGFMS diagnosis, but have no role in predicting medium-term clinical outcome.
FUS-CREB3L2 was capable of activating transcription from CD24 regulatory sequences in luciferase assays, suggesting an important role for the upregulation of this gene in LGFMS.
We present a case of an ossifying tumor of the perineum that required an open biopsy and fluorescent in situ hybridization testing for FUS and CREB3L2 for diagnosis as a variant of low-grade fibromyxoid sarcoma.
In accordance with previous studies, our case showed positive findings of FUS rearrangement, reinforcing the notion of a close relationship between low grade fibromyxoid sarcoma and SEF.
We evaluated cases of pure sclerosing epithelioid fibrosarcoma lacking areas of low-grade fibromyxoid sarcoma for FUS rearrangement to determine whether this entity could be related to low-grade fibromyxoid sarcoma.
Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma.
Fluorescent in situ hybridization (FISH) with a break-apart probe for FUS revealed the presence of a FUS gene rearrangement confirming the diagnosis of LGFMS.
This fusion has recently been described as a variant translocation in low-grade fibromyxoid sarcoma (LGFMS), a tumor more typically characterized by a recurrent t(7;16) chromosomal translocation, resulting in the fusion of FUS and CREB3L2 genes.
While the majority of LGFMS cases are characterized by a FUS-CREB3L1 fusion, both FUS-CREB3L2 and EWSR1-CREB3L1 fusions were recently demonstrated in a small number of LGFMS and SEF/LGFMS hybrid tumors.