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Nat Commun. 2015 Nov 17;6:8891. doi: 10.1038/ncomms9891.

Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney.

Author information

1
Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
2
Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.
3
Texas Children's Cancer Center, Houston, Texas 77030, USA.
4
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
5
Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
6
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
7
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
8
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
9
Department of Pathology and Laboratory Medicine, Children's Medical Center, Dallas, Texas 75390, USA.
10
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
11
Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
12
Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas 77030, USA.

Abstract

The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of 27 (85%) pediatric clear cell sarcomas of the kidney (CCSK) from two independent cohorts. We profile CCSK tumours using a combination of whole-exome, transcriptome and targeted sequencing. Identical ITD mutations are found in primary and relapsed tumour pairs but not in adjacent normal kidney or blood. Mutant BCOR transcripts and proteins are markedly upregulated in ITD-positive tumours. Transcriptome analysis of ITD-positive CCSKs reveals enrichment for PRC2-regulated genes and similarity to undifferentiated sarcomas harbouring BCOR-CCNB3 fusions. The discovery of recurrent BCOR ITDs defines a major oncogenic event in this childhood sarcoma with significant implications for diagnostic and therapeutic approaches to this tumour.

PMID:
26573325
PMCID:
PMC4660214
DOI:
10.1038/ncomms9891
[Indexed for MEDLINE]
Free PMC Article

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