Are EWSR1-NFATc2-positive sarcomas really Ewing sarcomas?

Abstract

Recently, Charville et al. [1] reported that EWSR1-rearranged fusion proteins mediate the expression of the paired-box transcription factor PAX7 in Ewing sarcoma. Based on an analysis of a published gene expression microarray dataset (accession code GSE60740), they state having identified PAX7 to be significantly overexpressed in Ewing sarcoma in comparison to CIC-DUX4-positive round cell sarcomas [1]. In that microarray analysis they compared CIC-DUX4-positive sarcomas with EWSR1-NFATc2-positive sarcomas, assuming that EWSR1-NFATc2-positive sarcomas belong to the family of Ewing sarcomas [1], which are typically characterized by EWSR1-ETS fusion oncogenes [2]. Accordingly, Charville et al. [1] summarized in a schematic EWSR1-FLI1-, EWSR1-ERG-, and EWSR1-NFATc2-positive sarcomas as “Ewing sarcoma,” referring to Szuhai et al. (2009) [3], and did not take into account more recent reports in the literature that EWSR1-NFATc2-positive sarcomas may constitute an own entity [2]. Comparison of the dataset (GSE60740) used by Charville et al. to a published transcriptome reference dataset of genetically defined EWSR1-ETS-positive Ewing sarcomas (GSE34620) [4] and 13 other malignancies that may constitute morphological mimics [5] shows that EWSR1-NFATc2-positive sarcomas do not cluster with any other analyzed tumor entity including EWSR1-ETS-positive Ewing sarcoma