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Quantification of genomic EWSR1 fusion sequences from plasma of Ewing sarcoma (EwS) patients for therapy monitoring and relapse detection
Background: Cell free circulating tumor DNA (ctDNA) has been shown to represent a biomarker in several common cancers of adulthood, taking advantage of recurrent point-mutations. We evaluated the use of the causative genomic fusion sequence as non-invasive tumor marker in pediatric EwS.
Method: Detectability and correlation of EWSR1-FLI1 copies with tumor burden were first explored in EwS xenograft mice. Subsequently, plasma samples from EwS patients were analyzed before and during chemotherapy using ddPCR.
Results: Kinetics of EWSR1-FLI1 levels are correlated with the tumor burden. Most EwS patients showed a fast reduction of ctDNA (negative at VIDE3). Relapse development was discovered by recurrence of increasing ctDNA levels.
Conclusions: Due to the high stability of genomic fusion sequences during clonal evolution they represent a promising serum marker for therapy assessment and ideal biomarker for relapse detection.