Next generation sequencing in synovial sarcoma reveals novel gene mutations

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// Myrella Vlenterie 1 , Melissa H.S. Hillebrandt-Roeffen 1 , Uta E. Flucke 2 , Patricia J.T.A. Groenen 2 , Bastiaan B.J. Tops 2 , Eveline J. Kamping 3 , Rolph Pfundt 3 , Diederik R.H. de Bruijn 3 , Ad H.M. Geurts van Kessel 3 , Han J.H.J.M. van Krieken 2 , Winette T.A. van der Graaf 1,4 and Yvonne M.H. Versleijen-Jonkers 1 1 Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands 2 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands 3 Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands 4 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK Correspondence to: Myrella Vlenterie, email: // Keywords : next generation sequencing, KRAS, CCND1, synovial sarcoma, chromosomal aberrations Received : June 21, 2015 Accepted : August 31, 2015 Published : September 22, 2015 Abstract Over 95% of all synovial sarcomas (SS) share a unique translocation, t(X;18), however, they show heterogeneous clinical behavior. We analyzed multiple SS to reveal additional genetic alterations besides the translocation. Twenty-six SS from 22 patients were sequenced for 409 cancer-related genes using the Comprehensive Cancer Panel (Life Technologies, USA) on an Ion Torrent platform. The detected variants were verified by Sanger sequencing and compared to matched normal DNAs. Copy number variation was assessed in six tumors using the Oncoscan array (Affymetrix, USA). In total, eight somatic mutations were detected in eight samples. These mutations have not been reported previously in SS. Two of these, in KRAS and CCND1, represent known oncogenic mutations in other malignancies. Additional mutations were detected in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4 . DNA alterations occurred more often in adult tumors. A distinctive loss of 6q was found in a metastatic lesion progressing under pazopanib, but not in the responding lesion. Our results emphasize t(X;18) as a single initiating event in SS and as the main oncogenic driver. Our results also show the occurrence of additional genetic events, mutations or chromosomal aberrations, occurring more frequently in SS with an onset in adults.

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