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Eisenhardt, Anja E.; Brugger, Zacharias; Lausch, Ute; Kiefer, Jurij; Zeller, Johannes; Runkel, Alexander; Schmid, Adrian; Bronsert, Peter; Wehrle, Julius; Leithner, Andreas; Liegl-Atzwanger, Bernadette; Giunta, Riccardo E.; Eisenhardt, Steffen U.; Braig, David

Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas

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  • Media type: E-Article
  • Title: Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas
  • Contributor: Eisenhardt, Anja E.; Brugger, Zacharias; Lausch, Ute; Kiefer, Jurij; Zeller, Johannes; Runkel, Alexander; Schmid, Adrian; Bronsert, Peter; Wehrle, Julius; Leithner, Andreas; Liegl-Atzwanger, Bernadette; Giunta, Riccardo E.; Eisenhardt, Steffen U.; Braig, David
  • imprint: MDPI AG, 2022
  • Published in: Cancers
  • Language: English
  • DOI: 10.3390/cancers14092078
  • ISSN: 2072-6694
  • Origination:
  • Footnote:
  • Description: <jats:p>Background: Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection. Methods: We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses SS18 (SYT) in chromosome 18 to SSX1 or SSX2 in chromosome x, and recurrent point mutations. In addition, patient-specific panels were designed from tumor exome sequencing. Both approaches were used to quantify ctDNA in patients’ plasma. Results: The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples (n = 11) from one patient collected over 3 years, with a patient-specific panel based on tumor exome sequencing, correlated with the clinical course, response to treatment and tumor volume. Conclusions: Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics.</jats:p>
  • Access State: Open Access