Liquid biopsies in pediatric solid tumors

Background

Despite advances in treatment and survival, mortality remains high for pediatric patients with solid tumors who develop metastatic or relapsed disease. Imaging technologies are currently the primary method for detecting complete remission; however, relapse occurs in a significant percentage of patients with various cancers like neuroblastomas, Ewing sarcomas, rhabdomyosarcomas, osteosarcomas, and renal tumors. After recurrence, treatment response is generally poor. To reduce invasive procedures and minimize risks associated with general anesthesia radiation exposure, liquid biopsies are emerging as a promising diagnostic and monitoring tool. These biopsies, which analyze blood or other body fluids, provide a less invasive alternative for detecting biomarkers such as circulating tumor cells, RNA and cell free DNA). In addiction to being less invasive, liquid biopsies help address the challenge   of spatial or (sub)clonal tumor heterogeneity.

Aims

• To investigate the clinical significance of minimal residual disease in bone marrow and blood in patients with neuroblastoma.

• To develop and investigate the clinical significance of cell free DNA tumor markers in patients with neuroblastoma and other pediatric solid tumors.

Project Outcomes

• van Zogchel, L.M.J., Decarolis, B., van Wezel, E.M. et al. (2024). Sensitive liquid biopsy monitoring correlates with outcome in the prospective international GPOH-DCOG high-risk neuroblastoma RT-qPCR validation study. J Exp Clin Cancer Res, 43, 331. doi: 10.1186/s13046-024-03261-y

• Lak, N.S.M., van Zogchel, L.M.J., Zappeij-Kannegieter, L. et al. (2023). Cell-Free DNA as a Diagnostic and Prognostic Biomarker in Pediatric Rhabdomyosarcoma. JCO Precision Oncology, (7). doi: 10.1200/PO.22.00113

• van Zogchel, L. M.J., Lak, N.S.M.,Gelineau, N.U. et.al. (2023). Targeted locus amplification to develop robust patient-specific assays for liquid biopsies in pediatric solid tumors. Frontiers in Oncology, 13. doi: 10.3389/fonc.2023.1124737

• van Zogchel, L.M.J., Lak, N.S.M., Verhagen, O.J.H.M. et al. (2021). Novel Circulating Hypermethylated RASSF1A ddPCR for Liquid Biopsies in Patients With Pediatric Solid Tumors. JCO Precision Oncology, 5(5):1738-1748. doi:10.1200/PO.21.00130

• Lobo, J., van Zogchel, L.M.J., Nuru, M.G., Gillis, A. J. M., van der Schoot, C. E., Tytgat, G. A. M., & Looijenga, L. H. J. (2021). Combining Hypermethylated RASSF1A Detection Using ddPCR with miR-371a-3p Testing: An Improved Panel of Liquid Biopsy Biomarkers for Testicular Germ Cell Tumor Patients. Cancers. 13(20):5228. doi: 10.3390/cancers13205228

• van Zogchel, L. M. J., Zappeij-Kannegieter, L., Javadi, A., Lugtigheid, M., Gelineau, N. U., Lak, N. S. M., Zwijnenburg, D. A., Koster, J., Stutterheim, J., van der Schoot, C. E., & Tytgat, G. A. M. (2021). Specific and Sensitive Detection of Neuroblastoma mRNA Markers by Multiplex RT-qPCR. Cancers, 13(1), 150. doi: 10.3390/cancers13010150

• Hochheuser, C., van Zogchel, L. M. J., Kleijer, M., Kuijk, C., Tol, S., van der Schoot, C. E., Voermans, C., Tytgat, G. A. M., & Timmerman, I. (2020). The Metastatic Bone Marrow Niche in Neuroblastoma: Altered Phenotype and Function of Mesenchymal Stromal Cells. Cancers, 12(11), 3231. doi: 10.3390/cancers12113231

• van Zogchel, L.M.J., van Wezel, E.M., van Wijk, J. et al. (2020). Hypermethylated RASSF1A as Circulating Tumor DNA Marker for Disease Monitoring in Neuroblastoma.  JCO Precision Oncology, 4:291-306. doi: 10.1200/PO.19.00261

• van Wezel, E.M., van Zogchel, L.M.J., van Wijk, J. et al. (2019). Mesenchymal Neuroblastoma Cells Are Undetected by Current mRNA Marker Panels: The Development of a Specific Neuroblastoma Mesenchymal Minimal Residual Disease Panel. JCO Precision Oncology, 3:1-11. doi: 10.1200/PO.18.00413

Team

• Prof.dr. M. Fiocco, Mathematical Institute Leiden University, Department of Biomedical Data Sciences Leiden University Medical Center & Princess Máxima Center for Pediatric Oncology 

• Prof. dr. C.E. van der Schoot, Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory of the Amsterdam UMC, Amsterdam, The Netherlands

• Prof. dr. G.A.M. Tytgat, Princess Máxima Center for Pediatric Oncology 

• Drs. L.M.J. van Zogchel, Princess Máxima Center for Pediatric Oncology and Department of Experimental Immunohematology, Sanquin Research and Landsteiner Laboratory of the Amsterdam UMC, Amsterdam, The Netherlands