EWSR1/FUS–CREBs-associates malignant epithelioid neoplasm

Fusions between EWSR1 or FUS with genes encoding for CREB-transcription factors family (ATF1, CREB1, and CREM) drives the pathogenesis of various tumor types spanning mesenchymal, neuroectodermal, and epithelial lineages.

Gene fusions constitute pivotal driver mutations often encoding aberrant chimeric transcription factors.

However, an increasing number of gene fusion events have been shown not to be histotype specific and shared among different tumor types, otherwise completely unrelated clinically or phenotypically.

One such remarkable example of chromosomal translocation promiscuity is represented by fusions between EWSR1 or FUS with genes encoding for CREB-transcription factors family (ATF1, CREB1, and CREM), driving the pathogenesis of various tumor types spanning mesenchymal, neuroectodermal, and epithelial lineages.

These findings expand the spectrum of tumors associated with CREB-related fusions, defining a novel malignant epithelioid neoplasm with an immunophenotype suggesting epithelial differentiation.

This entity appears to display hybrid features between angiomatoid fibrous histiocytoma ( cystic growth and lymphoid cuffing ) and epithelioid mesothelioma (peritoneal/pleural involvement, epithelioid phenotype, and cytokeratin and WT1 co-expression).

Paywall references

 EWSR1/FUS–CREB fusions define a distinctive malignant epithelioid neoplasm with predilection for mesothelial-lined cavities.

• https://www.nature.com/articles/s41379-020-0646-5