title: Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma.
abstract: OBJECTIVE
  Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about one third. No tumor-specific rearrangement has been identified, and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions.
  
  
  METHODS
  RNA-Seq, FISH, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas.
  
  
  RESULTS
  Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3' partner and either MED12 or CITED2 as the 5' partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before.
  
  
  CONCLUSIONS
  Our results suggest that PRDM10 fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden. jakob.hofvander@med.lu.se.
authors.forename: Jakob
authors.initials: J
authors.lastname: Hofvander
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Johnbosco
authors.initials: J
authors.lastname: Tayebwa
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Magnusson
authors.affiliation: Department of Orthopedics, Karolinska University Hospital, Solna, Sweden.
authors.forename: Otte
authors.initials: O
authors.lastname: Brosjö
authors.affiliation: Department of Pathology, Karolinska University Hospital, Solna, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Larsson
authors.affiliation: Department of Orthopedics, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Vult von Steyern
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D059786:Abnormal Karyotype; D004268:DNA-Binding Proteins / Q000235:genetics*; D050939:Gene Fusion / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D056892:Mediator Complex / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C486381:CITED2 protein, human; D004268:DNA-Binding Proteins; C460107:MED12 protein, human; D056892:Mediator Complex; C469414:PRDM10 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors