Clear cell sarcomas of the kidney are characterised by BCOR BCOR BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR – CCNB 3 BCOR BCOR – CCNB CCNB 3 gene fusion

摘要

Aims Clear cell sarcoma of the kidney ( CCSK ) is a rare paediatric renal malignant tumour. The majority of CCSK s have internal tandem duplications ( ITD s) of the BCOR gene, whereas a minority have the YWHAE – NUTM 2 gene fusion. A third ‘double‐negative’ ( DN ) category comprises CCSK s with neither BCOR ITD s nor YWHAE – NUTM 2 fusion. The aim of this study was to characterise 11 histologically diagnosed CCSK s immunohistochemically (with CCND 1, BCOR and CCNB 3 stains) and genetically. Methods and results By next‐generation sequencing, 10 cases (90.9%) had BCOR exon 15 ITD s, with positive BCOR immunoreactivity being found in four (36%) or eight (72%) cases, depending on the antibody clone. By reverse transcription polymerase chain reaction, none had the YWHAE – NUTM 2 fusion. The DN case had a BCOR – CCNB 3 fusion and strong nuclear CCNB 3 and BCOR immunoreactivity. Quantitative polymerase chain reaction showed markedly elevated BCOR expression in this case, whereas BCOR ITD cases had lower levels of elevated BCOR expression. Conclusions The majority of the CCSK s in our cohort had BCOR ITD s, and none had the YWHAE – NUTM 2 fusion. We verified the strong, diffuse cyclin D1 ( CCND 1) immunoreactivity in CCSK s described in recent reports. BCOR immunoreactivity was not consistently positive in all CCSK s with BCOR ITD s, and therefore cannot be used as a diagnostic immunohistochemical stain to identify BCOR ITD cases. The DN case was a BCOR – CCNB 3 fusion sarcoma. BCOR – CCNB 3 sarcoma is typically a primary bone sarcoma affecting male adolescents, and this is the first report of it presenting in a kidney of a young child as a CCSK . The full spectrum of DN CCSK s awaits more comprehensive characterisation.