title: FUS-CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1.
abstract: OBJECTIVE
  Low-grade fibromyxoid sarcoma (LGFMS) is typically characterized by the specific translocation t(7;16)(q33;p11) and the corresponding fusion gene FUS-CREB3L2. The present study aimed to extract LGFMS-specific, and putatively FUS-CREB3L2-dependent, gene expression patterns to learn more about the pathogenesis of this tumor.
  
  
  METHODS
  We carried out single nucleotide polymorphism (SNP) and global gene expression array analyses, and/or immunohistochemical (IHC) analyses on 24 LGFMS tumor biopsies. Tumor types that are important differential diagnoses to LGFMS were included as comparison in the gene and protein expression analyses. In addition, cells that stably expressed FUS-CREB3L2 were analyzed with gene expression array and the influence of FUS-CREB3L2 on gene expression was investigated in vitro.
  
  
  RESULTS
  The SNP array analysis detected recurrent microdeletions in association with the t(7;16) chromosomal breakpoints and gain of 7q in cases with ring chromosomes. Gene expression analysis clearly distinguished LGFMS from morphologically similar tumors and MUC4 was identified as a potential diagnostic marker for LGFMS by gene expression and IHC analysis. FOXL1 was identified as the top upregulated gene in LGFMS and CD24 was upregulated in both LGFMS tumors and FUS-CREB3L2 expressing cells. FUS-CREB3L2 was capable of activating transcription from CD24 regulatory sequences in luciferase assays, suggesting an important role for the upregulation of this gene in LGFMS.
  
  
  CONCLUSIONS
  The gene expression profile of LGFMS is distinct from that of soft tissue tumors with similar morphology. The data could be used to identify a potential diagnostic marker for LGFMS and to identify possible FUS-CREB3L2 regulated genes.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skane University Hospital, Lund University, Lund, Sweden. emely.moller@med.lu.se
authors.forename: Emely
authors.initials: E
authors.lastname: Möller
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
authors.forename: Linda
authors.initials: L
authors.lastname: Magnusson
authors.forename: Srinivas
authors.initials: S
authors.lastname: Veerla
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051927:CD24 Antigen / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000235:genetics; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D051927:CD24 Antigen; C497889:CD24 protein, human; C485618:CREB3L1 protein, human; C518609:CREB3L2 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C491001:FOXL1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D034702:RNA-Binding Protein FUS