Detection of BCOR gene rearrangement in Ewing-like sarcoma: an important diagnostic tool

Lan Li,Hairong Xu,Xiaoqi Sun,Hongtao Ye,Tingting Zhang,Ming Zhang,Shaoyu Chen,Lina Li,Xiaoyuan Huang,Yi Ding

doi:10.1186/s13000-021-01114-2

Abstract

BackgroundBCOR-CCNB3 sarcoma (BCS) is a group of undifferentiated small round cell sarcomas harboring the BCOR gene rearrangement which shares morphology with the Ewing sarcoma family as well as other malignant round blue cell tumors, thus making them difficult to diagnose. The aim of this study was to explore the role of molecular techniques in the diagnosis of BCS.MethodsTwenty-three cases of EWSR1 rearrangement-negative undifferentiated small round cell sarcomas (Ewing-like sarcoma) were analyzed for the presence of BCOR gene rearrangement by Fluorescence in situ hybridization (FISH) and Reverse Transcription -Polymerase Chain Reaction (RT-PCR). The clinicopathological features of the positive cases were also reviewed. Fifteen additional cases were used as negative controls.ResultsEight cases were found with BCOR gene rearrangement by FISH and reappraised as BCS. The patients ranged in age from 8 to 20 years old, with a male predominance (M:F = 6:2). All tumors were located in the lower extremities. The tumor locations were more common in bone (n = 6) than deep soft tissue (n = 2). Histologically, 7 of 8 tumors were predominately composed of spindle or ovoid cells. The tumor cells were usually arranged in solid hypercellular sheets without a distinct architectural pattern. IHC showed expression of TLE1 (100%), CCNB3 (88%), BCOR (71%). RT-PCR for BCOR-CCNB3 fusion transcript was positive in 7 of 8 cases. Pre-operative chemotherapy resulted in eradication of tumors in 5 patients after a follow-up of 7 to 42 months.ConclusionsEfficient diagnosis of BCOR rearranged sarcomas is achieved by the using a combination of FISH and RT-PCR assays.

Highlights

BCOR-CCNB3 sarcoma (BCS) is a group of undifferentiated small round cell sarcomas harboring the BCOR gene rearrangement which shares morphology with the Ewing sarcoma family as well as other malignant round blue cell tumors, making them difficult to diagnose
We investigated the prevalence of the BCOR-CCNB3 fusion in pediatric and adult undifferentiated small round cell sarcomas, using a combination of Fluorescence in situ hybridization (FISH) and reverse transcription (RT)-Polymerase Chain Reaction (PCR) and report on the clinical and histopathological features of eight patients with sarcomas harboring this fusion gene
Clinical and histological features Twenty-three cases of EWSR1 rearrangement-negative undifferentiated small round cell sarcomas were analyzed by FISH and Reverse Transcription -Polymerase Chain Reaction (RT-PCR) respectively

Summary

Introduction

BCOR-CCNB3 sarcoma (BCS) is a group of undifferentiated small round cell sarcomas harboring the BCOR gene rearrangement which shares morphology with the Ewing sarcoma family as well as other malignant round blue cell tumors, making them difficult to diagnose. Tumors harboring the BCOR-CCNB3 fusion appear to share some clinical and morphological overlap with the Ewing family of tumors, sequencing analysis has shown that the rearrangement involves a paracentric inversion on the short arm of chromosome X, resulting in the fusion of two genes BCOR and CCNB3 and resulting in the expression of CCNB3. We investigated the prevalence of the BCOR-CCNB3 fusion in pediatric and adult undifferentiated small round cell sarcomas, using a combination of FISH and RT-PCR and report on the clinical and histopathological features of eight patients with sarcomas harboring this fusion gene

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