PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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: Samuel E Jones; Emmy D G Fleuren; Jessica Frankum; Asha Konde; Chris T Williamson; Dragomir B Krastev; Helen N Pemberton; James Campbell; Aditi Gulati; Richard Elliott; Malini Menon; Joanna L Selfe; Rachel Brough; Stephen J Pettitt; Wojciech Niedzwiedz; Winette T A van der Graaf; Janet Shipley; Alan Ashworth; Christopher J Lord Journal: Cancer Res Date: 2017-10-16 Impact factor: 12.701
Authors: Joanna Przybyl; Magdalena Kowalewska; Anna Quattrone; Barbara Dewaele; Vanessa Vanspauwen; Sushama Varma; Sujay Vennam; Aaron M Newman; Michal Swierniak; Elwira Bakuła-Zalewska; Janusz A Siedlecki; Mariusz Bidzinski; Jan Cools; Matt van de Rijn; Maria Debiec-Rychter Journal: JCI Insight Date: 2017-06-02
Authors: Gabriel N Hortobagyi; David Chen; Martine Piccart; Hope S Rugo; Howard A Burris; Kathleen I Pritchard; Mario Campone; Shinzaburo Noguchi; Alejandra T Perez; Ines Deleu; Mikhail Shtivelband; Norikazu Masuda; Shaker Dakhil; Ian Anderson; Douglas M Robinson; Wei He; Abhishek Garg; E Robert McDonald; Hans Bitter; Alan Huang; Tetiana Taran; Thomas Bachelot; Fabienne Lebrun; David Lebwohl; José Baselga Journal: J Clin Oncol Date: 2015-10-26 Impact factor: 44.544
Authors: C Chakiba; P Lagarde; D Pissaloux; A Neuville; C Brulard; G Pérot; J M Coindre; P Terrier; D Ranchere-Vince; A Ferrari; P Collini; A J H Suurmeijer; J Y Blay; S A Terrisse; S Piperno-Neumann; G Averous; B Bui; D Orbach; A Italiano; F Chibon Journal: Ann Oncol Date: 2014-07-28 Impact factor: 32.976