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.
Highlights
Synovial sarcoma (SS) accounts for approximately 8% of all soft tissue sarcomas
For the screening of somatic mutations by means of generation sequencing, we included 26 tumors from 22 patients of whom sufficient tissue with matched normal tissue was available in the local tissue bank from our hospital pathology database
Seventy-seven % (n = 20) of the tumor samples were from chemotherapy naïve patients, three tumor samples were from patients treated with neo-adjuvant chemotherapy, one couple consisting of two metastatic lesions were derived from one patient treated with pazopanib, and one recurrence was from a localization previously treated with adjuvant radiotherapy
Summary
Synovial sarcomas occur at all ages and sites throughout the body, with a predilection for the extremities of young adults. Patients with a synovial sarcoma have a 5-year cancer-specific survival rate of 66%, with a remarkable better outcome for children as compared to adults [1]. Predicting tumor behavior has been attempted by relating survival to various tumor and patient characteristics. Several of these characteristics have been proven to be of negative prognostic value, including large tumor size, primary tumor location in non-extremities and older age at diagnosis. Metastatic disease is treated by palliative chemotherapy or by applying the angiogenesis inhibitor pazopanib, with limited survival benefit [3]
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