title: Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney.
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.
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Angshumoy
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Vijetha
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Zorman
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Fang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Haines
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: HarshaVardhan
authors.initials: H
authors.lastname: Doddapaneni
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Hampton
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: White
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Abhishek A
authors.initials: AA
authors.lastname: Bavle
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Nimesh R
authors.initials: NR
authors.lastname: Patel
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Eldin
authors.affiliation: Department of Pathology &Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Pathology, Texas Children's Hospital, Houston, Texas 77030, USA.|Texas Children's Cancer Center, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: M
authors.initials: M
authors.lastname: John Hicks
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.|Department of Pathology and Laboratory Medicine, Children's Medical Center, Dallas, Texas 75390, USA.|Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Leavey
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Stephen X
authors.initials: SX
authors.lastname: Skapek
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Amatruda
authors.affiliation: Texas Children's Cancer Center, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.|Division of Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, Texas 77030, USA.
authors.forename: Jed G
authors.initials: JG
authors.lastname: Nuchtern
authors.affiliation: Texas Children's Cancer Center, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Chintagumpala
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wheeler
authors.affiliation: Texas Children's Cancer Center, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Plon
authors.affiliation: Texas Children's Cancer Center, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Sumazin
authors.affiliation: Texas Children's Cancer Center, Houston, Texas 77030, USA.|Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.|Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: D Williams
authors.initials: DW
authors.lastname: Parsons
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D020440:Gene Duplication; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018227:Sarcoma, Clear Cell / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D020080:Tandem Repeat Sequences
chemical_list: C411984:BCOR protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins