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

Autor: Eisenhardt AE; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Brugger Z; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Lausch U; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Kiefer J; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Zeller J; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Runkel A; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Schmid A; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Bronsert P; Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; Tumorbank Comprehensive Cancer Center Freiburg, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Wehrle J; Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Leithner A; Department of Orthopedics and Trauma, Medical University of Graz, 8036 Graz, Austria., Liegl-Atzwanger B; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria., Giunta RE; Division of Hand, Plastic and Aesthetic Surgery, University Hospital, Ludwig Maximilian University of Munich, 80336 Munich, Germany., Eisenhardt SU; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany., Braig D; Department of Plastic and Hand Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.; Division of Hand, Plastic and Aesthetic Surgery, University Hospital, Ludwig Maximilian University of Munich, 80336 Munich, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Apr 21; Vol. 14 (9). Date of Electronic Publication: 2022 Apr 21.
DOI: 10.3390/cancers14092078
Abstrakt: 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.
Databáze: MEDLINE
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