title: Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas.
abstract: OBJECTIVE
  Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.
  
  
  METHODS
  One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.
  
  
  RESULTS
  CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
  
  
  CONCLUSIONS
  Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.
authors: Institut Nationalde la Santé et de la Recherche Médicale (INSERM) U916-Institut Bergonie, France.
authors: Pauline
authors: P
authors: Lagarde
authors: Joanna
authors: J
authors: Przybyl
authors: Céline
authors: C
authors: Brulard
authors: Gaëlle
authors: G
authors: Pérot
authors: Gaelle
authors: G
authors: Pierron
authors: Olivier
authors: O
authors: Delattre
authors: Raf
authors: R
authors: Sciot
authors: Agnieszka
authors: A
authors: Wozniak
authors: Patrick
authors: P
authors: Schöffski
authors: Philippe
authors: P
authors: Terrier
authors: Agnès
authors: A
authors: Neuville
authors: Jean-Michel
authors: JM
authors: Coindre
authors: Antoine
authors: A
authors: Italiano
authors: Daniel
authors: D
authors: Orbach
authors: Maria
authors: M
authors: Debiec-Rychter
authors: Frédéric
authors: F
authors: Chibon
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D043171:Chromosomal Instability; D056915:DNA Copy Number Variations; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C509224:CDCA2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C502598:KIF14 protein, human; D016547:Kinesins