Same-day, multiplexed, high-accuracy targeted liquid biopsy approach for low-tumor content treatment response monitoring
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Motivation:
- Pediatric brain tumor diagnostics can be difficult: Brain tumors make up a significant proportion of pediatric cancers. However, due to their sensitive location, many difficulties exist in providing effective diagnostics, treatments, and treatment response monitoring for these patients. MRIs can be difficult to interpret due to diffuse disease and radiation induced swelling can masquerade as tumor progression (pseudoprogression), further complicating interpretation.
- Quantitative liquid-biopsy can be used to monitor treatment response: Prior work in our lab showed that same-day nanopore amplicon sequencing of cerebro-spinal fluid could aid in treatment response monitoring[1]. However, CSF is difficult to gather in pediatric patients — usually requiring a site visit and general anesthesia—increasing patient and family burden.
Research questions:
- Proof-of-concept: Can a two-step amplification approach capture, amplify, and concatemerize multiple narrow cell-free DNA targets?
- Speed: Can we perform same-day molecular diagnostics on cell-free DNA?
- Accuracy: How does our diagnostic compare to gold-standard methods (e.g. ddPCR genotyping)?