Rationale for Early Detection of EWSR1 Translocation-Associated Sarcoma Biomarkers in Liquid Biopsy

SIMPLE SUMMARY: Tumour cells often spread from the primary site to new tissues in a process known as metastasis. It has been demonstrated that there is a relationship between the number of circulating tumour cells in the blood and the tumour burden in patients with some forms of sarcoma, which is a cancer of bone and connective tissue. Sarcomas have a particular bias towards metastasis via the blood stream, which is able to be sampled relatively non-invasively, and many forms of sarcoma have well-characterised biomarkers that distinguish them from other blood cells. These characteristics potentiate the use of blood for ‘liquid biopsies’ for patients who are in remission, to detect a relapse as early as possible. This review summarises developments for sarcomas that are associated with the translocation of EWSR1 and similar genes. ABSTRACT: Sarcomas are mesenchymal tumours that often arise and develop as a result of chromosomal translocations, and for several forms of sarcoma the EWSR1 gene is a frequent translocation partner. Sarcomas are a rare form of malignancy, which arguably have a proportionally greater societal burden that their prevalence would suggest, as they are more common in young people, with survivors prone to lifelong disability. For most forms of sarcoma, histological diagnosis is confirmed by molecular techniques such as FISH or RT-PCR. Surveillance after surgical excision, or ablation by radiation or chemotherapy, has remained relatively unchanged for decades, but recent developments in molecular biology have accelerated the progress towards routine analysis of liquid biopsies of peripheral blood. The potential to detect evidence of residual disease or metastasis in the blood has been demonstrated by several groups but remains unrealized as a routine diagnostic for relapse during remission, for disease monitoring during treatment, and for the detection of occult, residual disease at the end of therapy. An update is provided on research relevant to the improvement of the early detection of relapse in sarcomas with EWSR1-associated translocations, in the contexts of biology, diagnosis, and liquid biopsy.