Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Eisenhardt, AE; Brugger, Z; Lausch, U; Kiefer, J; Zeller, J; Runkel, A; Schmid, A; Bronsert, P; Wehrle, J; Leithner, A; Liegl-Atzwanger, B; Giunta, RE; Eisenhardt, SU; Braig, D.
Genotyping of Circulating Free DNA Enables Monitoring of Tumor Dynamics in Synovial Sarcomas.
Cancers (Basel). 2022; 14(9): 2078
Doi: 10.3390/cancers14092078
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- Co-Autor*innen der Med Uni Graz
- Leithner Andreas
- Liegl-Atzwanger Bernadette
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- Abstract:
- 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.
- Find related publications in this database (Keywords)
- soft tissue sarcoma
- synovial sarcoma
- next-generation sequencing
- targeted sequencing
- circulating tumor DNA
- ctDNA
- liquid biopsy
- diagnostic biomarker