Patients with synovial sarcoma could greatly benefit from non-invasive assays for improved evaluation of response to treatment or early detection of disease recurrence. Our results, together with the report of Mihály et al., show that the liquid biopsy approach based on detection of
SS18-SSX1/2 fusion transcript alone is not sensitive enough in patients with synovial sarcoma. We have previously demonstrated a similar low sensitivity of CTC detection based on the analysis of
EWS-FLI1 and
EWS-ERG fusion transcripts in patients with Ewing sarcoma [
2]. In that study we detected CTCs only in 9% (3/34) of patients. Given this low rate of CTC detection in translocation-related sarcomas, we propose that other markers in peripheral blood, such as circulating tumor DNA (ctDNA), may be more clinically useful for an improved prognostication, molecular profiling, and surveillance of sarcoma patients. We have recently demonstrated that simultaneous detection of copy number changes and point mutations in ctDNA increased the number of molecular markers that can be monitored in plasma and may be clinically useful in leiomyosarcoma [
4]. Synovial sarcomas also demonstrate certain genomic aberrations that could potentially be detectable in plasma DNA. For example, we previously reported that a subset of synovial sarcomas show extensive DNA copy number alterations that could be used as a marker in ctDNA in patients with an increased genomic instability in their tumors [
5]. The Cancer Genome Atlas study has also demonstrated a unique DNA methylation profile of synovial sarcomas compared to the other types of sarcomas, and methylation patterns could also be profiled in ctDNA [
6]. Thus, a strategy similar to the one that we applied in leiomyosarcoma for an integrated profiling of different classes of genomic aberrations in ctDNA could be considered also in patients with synovial sarcoma.