Minimal residual disease detection in Ewing sarcoma using an ultrasensitive patient-specific liquid biopsy assay
Mentor Name: Brian Crompton
Ewing Sarcoma is the second most common bone cancer in adolescents and young adults. Although cure rates in children with localized disease approach 75%, treatment has significant toxicity. Circulating tumor DNA (ctDNA) found in blood of patients with Ewing sarcoma has shown promise as an early prognostic biomarker and predictive marker of treatment response. However, more sensitive assays are needed for detection of minimal residual disease (MRD) during treatment and off-treatment surveillance. In this project, we will leverage a patient-specific approach to detect ctDNA as a measure of MRD in patients recently enrolled in a prospective early phase trial. Oncogenic fusions that drive some pediatric cancers, such as Ewing Sarcoma, are expressed from DNA-level translocations that have intronic breakpoints, which are unique to every patient. Disease-specific hybrid capture assays can detect these patient-specific breakpoints in tumor samples or plasma samples with high ctDNA content. Once these breakpoints are identified, droplet digital polymerase chain reaction (ddPCR), using patient-specific primer sets, can detect the presence of ctDNA when it makes up as little as 0.01% of the total cell-free DNA in a plasma sample.
