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Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney

Nature Genetics volume 47, pages 861–863 (2015)Cite this article

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Abstract

Clear cell sarcoma of the kidney (CCSK) is one of the major pediatric renal neoplasms, but its associated genetic abnormalities are largely unknown. We identified internal tandem duplications in the BCOR gene (BCL6 corepressor) affecting the C terminus in 100% (20/20) of CCSK tumors but in none (0/193) of the other pediatric renal tumors. CCSK tumors expressed only an aberrant BCOR allele, indicating a close correlation between BCOR aberration and CCSK tumorigenesis.

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Figure 1: BCOR aberration in CCSK.

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Acknowledgements

This work was supported in part by the Grant from the National Center for Child Health and Development (24-4, 26-20), grants from the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO; 10-41, 10-42, 10-43, 10-44, 10-45), and a research program of the Project for Development of Innovative Research on Cancer Therapeutics (11035153) and Tailor-Made Medical Treatment Program (BioBankJapan), Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. Hajime Okita & Shingo Akimoto

    Present address: Present addresses: Department of Pathology, Keio University School of Medicine, Tokyo, Japan (H.O.) and Department of Surgery, Keio University School of Medicine, Tokyo, Japan (S.A.).,

Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan

    Hitomi Ueno-Yokohata, Hajime Okita, Keiko Nakasato, Shingo Akimoto & Nobutaka Kiyokawa

  2. Central Institute for Experimental Animals, Kawasaki, Japan

    Jun-ichi Hata

  3. Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan

    Tsugumichi Koshinaga

  4. Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    Masahiro Fukuzawa

Authors
  1. Hitomi Ueno-Yokohata
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Contributions

H.U.-Y. and H.O. designed the study. H.U.-Y., H.O., K.N. and S.A. performed the experiments. H.O. and J.H. conducted a pathological review. T.K. and M.F. provided patient materials. H.U.-Y., H.O. and N.K. wrote the manuscript.

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Correspondence to Hajime Okita.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Histopathological features of CCSK.

Hematoxylin-eosin staining shows typical histopathological features of CCSK. Scale bar, 100 µm.

Supplementary Figure 2 Genomic sequence alignment of wild-type and aberrant BCOR.

Genomic sequences corresponding to 5,068–5,268 nt of BCOR (CCDS48093.1) are aligned.

Supplementary Figure 3 BCOR expression in pediatric renal tumors and kidney.

(a) Quantitative RT-PCR of BCOR. The beeswarm and box plots present relative values of BCOR expression normalized with ACTB. (b) Two P values were calculated by pairwise comparisons using the Wilcoxon rank-sum test with the methods of Bonferroni and FDR.

Supplementary Figure 4 Western blot detection of BCOR protein expression in kidney, CCSK and other pediatric renal tumors.

Top, BCOR (arrowhead, full length). Bottom, lamin A/C (large fragment, lamin A; small fragment, lamin C). M, pre-stained protein marker (Broad Range, Nacalai Tesque); 1, HEK293; 2, Kidney6; 3, Kidney7; 4, CCSK8; 5, CCSK13; 6, RTK4; 7, RTK7; 8, CMN5; 9, CMN6; 10, Wilms43; 11, Wilms53.

Supplementary Figure 5 Immunohistochemical staining of BCOR in CCSK and non-CCSK tissues.

Scale bar, 100 µm.

Supplementary Figure 6 Immunoblotting and soft agar colony formation assay of HEK293 cells expressing exogenous BCORs.

(a) Detection of endogenous and exogenous BCOR proteins in HEK293 cells. Top, BCOR (arrowhead, full length). Bottom, lamin A/C (large fragment, lamin A; small fragment, lamin C). Lane 1, empty vector; lane 2, wild-type BCOR; lane 3, mutant 1 BCOR; lane 4, mutant 2 BCOR. (b) Soft agar colony formation assay with HEK293 cells expressing exogenous BCOR proteins. Error bars, s.e.m. *P < 0.05 (Welch’s t test, two-sided). (c) Images are the magnified center part (1.5 mm2) of wells.

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Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Tables 1 and 2. (PDF 915 kb)

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Ueno-Yokohata, H., Okita, H., Nakasato, K. et al. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet 47, 861–863 (2015). https://doi.org/10.1038/ng.3338

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