Clear cell sarcomas of kidney are characterized by BCOR gene abnormalities including exon 15 internal tandem duplications and BCOR-CCNB3 gene fusion

Abstract

Aims

Clear cell sarcoma of kidney (CCSK) is a rare paediatric renal malignant tumour. The majority of CCSKs have internal tandem duplications (ITD) of the BCOR gene while a minority has the YWHAE-NUTM2 gene fusion. A third 'double-negative' (DN) category comprises CCSKs with neither BCOR ITD nor YWHAE-NUTM2 fusion. The aim of this study was to characterize 11 histologically diagnosed CCSKs immunohistochemically (with CCND1, BCOR and CCNB3 stains), and genetically.

Methods and results

By next-generation sequencing, 10 cases (90.9%) had BCOR exon 15 ITD, with positive BCOR immunoreactivity in 4 (36%) or 8 (72%) cases depending on antibody clone. By RT-PCR, none had the YWHAE-NUTM2 fusion. The DN case had a BCOR-CCNB3 fusion and strong nuclear CCNB3 and BCOR immunoreactivity. Quantitative PCR showed markedly elevated BCOR gene expression in this case whereas BCOR ITD cases had lower elevations.

Conclusions

The majority of the CCSKs in our cohort have BCOR ITD, and none have the YWHAE-NUTM2 gene fusion. We verify the strong, diffuse cyclin D1 (CCND1) immunoreactivity in CCSKs described in recent reports. BCOR immunoreactivity is not consistently positive in all CCSKs with BCOR ITD and therefore cannot be used as a diagnostic immunohistochemical stain to identify BCOR ITD cases. The DN case is a BCOR-CCNB3 fusion sarcoma. Typically a primary bone sarcoma affecting male adolescents, this is the first report of a BCOR-CCNB3 sarcoma presenting in a kidney of a young child as a CCSK. The full spectrum of DN CCSKs awaits more comprehensive characterization.

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