Premium
Clear cell sarcomas of the kidney are characterised by BCOR gene abnormalities, including exon 15 internal tandem duplications and BCOR – CCNB 3 gene fusion
Author(s) -
Wong Meng K,
Ng Cedric C Y,
Kuick Chik H,
Aw Sze J,
Rajasegaran Vikneswari,
Lim Jing Q,
Sudhanshi Jain,
Loh Eva,
Yin Minzhi,
Ma Jing,
Zhang Zhongde,
Iyer Prasad,
Loh Amos H P,
Lian Derrick W Q,
Wang Shi,
Goh Shaun G H,
Lim Tse H,
Lim Alvin S T,
Ng Tony,
Goytain Angela,
Loh Alwin H L,
Tan Puay H,
Teh Bin T,
Chang Kenneth T E
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13366
Subject(s) - fusion gene , immunohistochemistry , sarcoma , pathology , medicine , biology , cancer research , gene , genetics
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.