title: Whole transcriptome sequencing identifies BCOR internal tandem duplication as a common feature of clear cell sarcoma of the kidney.
abstract: OBJECTIVE
  Clear cell sarcoma of the kidney (CCSK) is a rare pediatric renal tumor that is frequently difficult to distinguish among other childhood renal tumors due to its histological heterogeneity. This work evaluates genetic abnormalities carried by a series of CCSK samples by whole transcriptome sequencing (WTS), to identify molecular biomarkers that could improve the diagnostic process.
  
  
  METHODS
  WTS was performed on tumor RNA from 8 patients with CCSK. Bioinformatic analysis, with implementation of a pipeline for detection of intragenic rearrangements, was executed. Sanger sequencing and gene expression were evaluated to validate BCOR internal tandem duplication (ITD).
  
  
  RESULTS
  WTS did not identify any shared SNVs, Ins/Del or fusion event. Conversely, analysis of intragenic rearrangements enabled the detection of a breakpoint within BCOR transcript recurrent in all samples. Three different in-frame ITD in exon15 of BCOR, were detected. The presence of the ITD was confirmed on tumor DNA and cDNA, and resulted in overexpression of BCOR.
  
  
  CONCLUSIONS
  WTS coupled with specific bioinformatic analysis is able to detect rare genetic events, as intragenic rearrangements. ITD in the last exon of BCOR is recurrent in all CCSK samples analyzed, representing a valuable molecular marker to improve diagnosis of this rare childhood renal tumor.
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.|Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.affiliation: Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Fraia
authors.initials: F
authors.lastname: Melchionda
authors.affiliation: Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.affiliation: Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Fois
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Indio
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.|Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Urbini
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Chiara Giusy
authors.initials: CG
authors.lastname: Genovese
authors.affiliation: Soft Tissue and Bone Pathology, Histopathology, and Pediatric Pathology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Collini
authors.affiliation: Pathology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Salfi
authors.affiliation: Department of Pediatric Hematology and Oncology, Istituto G. Gaslini, Genova, Italy.
authors.forename: Marilina
authors.initials: M
authors.lastname: Nantron
authors.affiliation: Pediatric Hematology and Oncology Unit, A.R.N.A.S. Civico, Di Cristina and Benfratelli Hospital, Palermo, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: D'Angelo
authors.affiliation: Pediatric Oncology Unit, Department of Hematology and Pediatric Onco-Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Spreafico
authors.affiliation: Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pession
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015203:Reproducibility of Results; D018227:Sarcoma, Clear Cell / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity; D020080:Tandem Repeat Sequences / Q000235:genetics*; D059467:Transcriptome
chemical_list: C411984:BCOR protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins
keywords: BCOR; CCSK; whole transcriptome sequencing