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Diagnostic Biomarkers for Soft Tissue Sarcomas

Univ.-Prof. Steffen U. Eisenhardt

PD Dr. David Braig

PD Dr. David Braig

Dr. Anja Eisenhardt

Dr. Alexander Runkel

Dr. Adrian Schmid

About 50% of soft tissue sarcomas relapse after treatment of the primary tumour. Early detection and treatment of local recurrence or metastasis can significantly improve long-term disease control and survival. Most recurrences develop within 2-3 years after treatment. Closely spaced and efficient follow-up strategies are therefore mandatory to detect recurrence at an early stage.

Current follow-up strategies, which consist of a physical examination and various imaging modalities, lack evidence and are expensive, time consuming and associated with radiation exposure.

Our research aims to develop non-invasive strategies for the diagnosis of soft tissue sarcomas. We want to distinguish patients with active disease from healthy persons by liquid biopsy. Different tumour-induced changes in the peripheral blood of patients with soft tissue sarcomas are targeted. We recently discovered a miRNA signature in the peripheral blood of patients with Synovial Sarcomas, which distinguished them from healthy persons and other sarcoma entities and established sensitive methods for the detection of sarcoma associated fusion genes.

Present research focuses on the detection of free circulating tumour DNA (ctDNA). Highly sensitive methods enable the quantification of tumour-derived ctDNA in the peripheral blood due to tumour-specific DNA alterations. The amount of ctDNA is further analysed in respect to the tumour volume, which is obtained by 3D volume rendering of MRI and CT scans.

 

 

1. Eisenhardt AE, Schmid A, Esser J, Brugger Z, Lausch U, Kiefer J, Braig M, Runkel A, Wehrle J, Claus R, Bronsert P, Leithner A, Liegl-Atzwanger B, Zeller J, Papini R, von Laffert M, Pfitzner BM, Koulaxouzidis G, Giunta RE, Eisenhardt SU, Braig D. (2022).

Targeted next-generation sequencing of circulating free DNA enables non-invasive tumor detection in myxoid liposarcomas.

Molecular Cancer 21, 50 (2022).

 

2. Braig D, Becherer C, Bickert C, Braig M, Claus R, Eisenhardt AE, Heinz J, Scholber J, Herget GW, Bronsert P, Fricke A, Follo M, Stark GB, Bannasch H, Eisenhardt SU. (2019).

Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas.

Int J Cancer. 2019 Aug 15;145(4):1148-1161.

 

3. Zeller J, Kiefer J, Braig D, Winninger O, Dovi-Akue D, Herget GW, Stark GB, Eisenhardt SU (2019).

Efficacy and Safety of Microsurgery in Interdisciplinary Treatment of Sarcoma Affecting the Bone.

Front Oncol. 2019 Nov 26;9:1300.

 

4. Fricke A, Cimniak AFV, Ullrich PV, Becherer C, Bickert C, Pfeifer D, Heinz J, Stark GB, Bannasch H, Braig D, Eisenhardt SU (2018).

Whole Blood miRNA Expression Analysis Reveals miR-3613-3p As A Potential Biomarker For Dedifferentiated Liposarcoma.

Cancer Biomarkers. 2018 Apr 9. doi: 10.3233/CBM-170496.

 

5. Fricke A, Ullrich PV, Cimniak AFV, Becherer C, Follo M, Heinz J, Scholber J, Herget GW, Hauschild O, Wittel UA, Stark GB, Bannasch H, Braig D, Eisenhardt SU (2017).

Levels of activated platelet-derived microvesicles in patients with soft tissue sarcoma correlate with an increased risk of venous thromboembolism.

BMC Cancer. 2017; 7;17(1):527.

 

6. Fricke A, Ullrich PV, Cimniak AF, Follo M, Nestel S, Heimrich B, Nazarenko I, Stark GB, Bannasch H, Braig D, Eisenhardt SU (2016).

Synovial Sarcoma Microvesicles Harbor the SYT-SSX Fusion Gene Transcript: Comparison of Different Methods of Detection and Implications in Biomarker Research.

Stem Cells International. 2016; 6146047.

 

7. Fricke A, Ullrich PV, Heinz J, Pfeifer D, Scholber J, Herget GW, Hauschild O, Bronsert P, Stark GB, Bannasch H, Eisenhardt SU, Braig D (2015).

Identification of a blood-borne miRNA signature of synovial sarcoma.

Molecular Cancer. 2015; 7;14:151.

 

8. Kiefer J, Braig D, Stark GB, Eisenhardt SU (2020)

Liquid Biopsy-Diagnostik bei Sarkomen.

 JOURNAL ONKOLOGIE 9/2020

Fig. 1: Blood-borne miRNA signature of synovial sarcoma. Hierarchical clustering separated synovial sarcoma samples from healthy controls. Further information can be obtained from https://www.ncbi.nlm.nih.gov/pubmed/26250552.

Fig. 2: Simultaneous detection of tumour DNA from a synovial sarcoma harbouring a SYT-SSX Fusion (blue droplets) within the background of human wild-type DNA (green) by droplet digital PCR.

Fig. 3: 3D volume rendering of a MRI scan from a patient with a soft tissue sarcoma