The GIST and Sarcoma Journal ���� ���������������������� ���������������������������������������������������������������� ���������������������������������������������������������������� Editor’s note: This report is adapted from Namløs HM, Zaikova O,Bjerkehagen B. Use of liquid biopsies to monitor disease progression in a sarcoma patient: a case report. BMC Cancer. 2017;17:29. DOI: 10.1186/s12885-016-2992- 8. Additional material is included from PubMed sources. lthough circulating tumor cells can be detected from the peripheral blood of cancer patients—and their prognostic value has been well established for metastatic colorectal, breast, and prostate cancer—information on their presence in patients affected by sarcomas is scarce. The discovery of EpCAM mRNA expression in different sarcoma cell lines and in a small cohort of metastatic sarcoma patients supports further investigations on these rare tumors to deepen the importance of circulating tumor cell (CTC) isolation.1 Although it is not clear whether EpCAM expression might be originally present on tumor sarcoma cells or acquired during the mesenchymal-epithelial transition, the discovery of EpCAM on circulating sarcoma cells opens a new scenario in CTC detection in patients affected by a rare mesenchymal tumor. Sarcomas are relatively rare but particularly lethal tumors, with over 5,800 deaths per year in the United States,2 accounting for about 1% of all adult cancers and approximately 20% of pediatric solid malignancies.3 More than 50 subtypes of soft tissue malignant tumors of mesenchymal origin have been documented.4,5 The diagnosis is performed by hematoxylin and eosin staining of sections and immunohistochemistry. To date, radiographic imaging and PET are performed to detect recurrence and metastasis. Advances in different technologies are transforming this picture. There are now new techniques available for molecular characterization of such tumor types Analyses such as Polymerase Chain Reaction (PCR), fluorescent in situ hybridization (FISH), Real-Time PCR, and next-generation sequencing (NGS) or the presence of reciprocal chromosomal translocations and fusion genes may be useful for diagnosis and treatment of sarcoma patients.6 Since most soft tissue sarcomas use the hematogenous dissemination to metastasize to lungs, liver, bones, and subcutaneous tissue whereas a small percentage may spread to lymph nodes,7,8 it is possible to isolate and characterize circulating tumor cells (CTCs) from whole blood based on their biological and/or physical properties.9 Furthermore, CTCs provide through their molecular evaluation an example of “liquid biopsy” useful for cancer patient care.10 The circulating cell-free tumor DNA (ctDNA) has been shown to contain the various tumor-specific alterations seen in the primary and metastatic tumors, and may more accurately represent the genetic profile of the whole tumor mass compared to DNA from a single biopsy of a heterogeneous lesion.11 By repeated sampling of liquid biopsies, somatic mutations identified in cfDNA can be used as unique noninvasive tumor-specific biomarkers for monitoring tumor burden throughout the disease course. Similar procedures are now in use for screening of fetal genetic aberrations using the mother’s blood, and in several cases aberrations from malignant tumors have been detected presymtomatic in pregnant women.12 Several reports have demonstrated that high-throughput sequencing of cfDNA may be used for prognosis and molecular stratification, early detection of recurrence and metastasis, monitoring response to treatment and identification of resistance mechanisms.13 Sequencing of cfDNA has been performed for cancers like colorectal, ovarian and breast, showing that the level of tumor-specific mutations reflects the course of the disease and the treatment response. 14-16 Sarcomas make up a heterogeneous group of malignant tumors of mainly mesenchymal origin. The overall five-year survival of all soft tissue sarcoma patients is approximately 70%,17,18 and about 75% of soft tissue sarcomas are highly malignant. Soft tissue sarcomas often recur locally and/or metastasize, and the median time to local recurrence is around 1-1½ year and to metastasis about 1 year,19,20 both decreasing long-term survival. From a molecular genetics perspective, sarcomas are genetic diverse and may have numerous somatic mutations.21 The use of high-throughput sequencing of cfDNAs longitudinally collected during disease progression, making simultaneous screening for multiple mutations during the disease course possible, has not yet been reported for sarcomas. As part of an ongoing prospective study,1 the study col- A
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