Recurrent EWSR1-CREB3L1 Gene Fusions in Sclerosing Epithelioid Fibrosarcoma
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
The American journal of surgical pathology
Abstract
Sclerosing epithelioid fibrosarcoma (SEF) and lowgrade
fibromyxoid sarcoma (LGFMS) are 2 distinct types of
sarcoma, with a subset of cases showing overlapping morphologic
and immunohistochemical features. LGFMS is characterized
by expression of the MUC4 protein, and about 90% of
cases display a distinctive FUS-CREB3L2 gene fusion. In addition,
SEF is often MUC4 positive, but is genetically less well
studied. Fluorescence in situ hybridization (FISH) studies have
shown involvement of the FUS gene in the majority of so-called
hybrid LGFMS/SEF and in 10% to 25% of sarcomas with pure
SEF morphology. In this study, we investigated a series of 10
primary tumors showing pure SEF morphology, 4 cases of
LGFMS that at local or distant relapse showed predominant
SEF morphology, and 1 primary hybrid LGFMS/SEF. All but 1
case showed diffuse expression for MUC4. Using FISH, reverse
transcription polymerase chain reaction, and/or mRNA sequencing
in selected cases, we found recurrent EWSR1-CREB3L1
fusion transcripts by reverse transcription polymerase chain reaction
in 3/10 pure SEF cases and splits and deletions of the
EWSR1 and/or CREB3L1 genes by FISH in 6 additional cases.
All 5 cases of LGFMS with progression to SEF morphology or
hybrid features had FUS-CREB3L2 fusion transcripts. Our results
indicate that EWSR1 and CREB3L1 rearrangements are
predominant over FUS and CREB3L2 rearrangements in pure
SEF, highlighting that SEF and LGFMS are different tumor
types, with different impacts on patient outcome.
Description
Keywords
Sclerosing epithelioid fibrosarcoma, Low-grade fibromyxoid sarcoma, Hybrid, Gene fusion, EWSR1, FUS, CREB3L, CREB3L
Citation
Arbajian, E., Puls, F., Magnusson, L., Thway, K., Fisher, C., Sumathi, V. P., ... & Mertens, F. (2014). Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. The American journal of surgical pathology, 38(6), 801-808.