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15A. Liquid biopsies in neuroblastoma, focus on cell-free DNA

Liquid biopsy approaches are promising in adult cancer. However, translation to pediatric cancer is challenging, as all pediatric cancers are rare diseases with significantly different genetic aberrations and typically small sampling volumes. Neuroblastoma, the most common extracranial pediatric tumor, is extremely heterogenous with copy number alterations, chromoplexy and chromothripsis and requires more complex detection strategies than multiplexed panels for specific recurrent mutations. In an era where molecular testing and molecularly guided treatments are available, a 40% 3-year overall-survival in high-risk neuroblastoma is unacceptable. This underlines the urgent need to design neuroblastoma-specific liquid biopsy approaches.

Liquid biopsies are minimally invasive, allowing sequential sampling and enable the detection of all circulating tumor-derived DNA (ctDNA) clones from the tumor and its metastases, overcoming the well-described spatial tumor heterogeneity. Reliable detection of trace amounts of fragmented ctDNA from a routine blood-draw remains a major technical challenge. Thorough analytical evaluation of ctDNA assays to define diagnostic limits, assess reproducibility and identify key experimental variables that impact performance, are urgently needed.

The ultimate aim of this project is to validate the clinical applicability of liquid biopsies and to define which markers will be used for decision making in clinical trials

In this project we will study circulating DNA detection in paired tumor-liquid biopsies to evaluate plasma-based detection of diagnostic & prognostic DNA aberrations as a simple molecular test for tumor presence that can be applied anytime during the course of patient care/monitoring.

 

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