CRTC1–SS18 Fusion Sarcoma With Aberrant Anaplastic Lymphoma Kinase Expression

Abstract

Undifferentiated small round cell sarcoma (USRCS) represents a highly heterogeneous group of tumors. A variety of specific gene fusions of USRCS have been reported, including CIC–FOXO4, CIC–NUTM1, BCOR–MAML3, and ZC3H7B–BCOR. Here we report a case of sarcoma harboring a rare recurrent CRTC1–SS18 gene fusion, which was considered as USRCS previously. This sarcoma was composed of nests of small round cells encapsulated in a fibrous stroma. Foci of necrosis and hemorrhage were observed in the tumor. Immunohistochemistry for anaplastic lymphoma kinase showed diffuse positivity. RNA-seq results revealed a chromosomal translocation of CRTC1 gene exon 1 on chromosome 19 with SS18 gene exon 2 on chromosome 18. Thereafter, fluorescence in-situ hybridization confirmed the presence of SS18 gene and CRTC1 gene break-apart, which manifested as the splitting of red and green signals into 2 parts. A previous study showed that CRTC1–SS18 fusion sarcoma and EWSR1–CREB1 fusion angiomatoid fibrous histiocytoma were clustered close in the expression profile. However, whether CRTC1–SS18 fusion sarcomas represent a high malignancy has been a matter of debate. Our study is a worthy addition to the series of rare rearrangements associated with sarcomas and may be of therapeutic relevance.