Use of liquid biopsies in pediatric solid tumors
Diagnostic and therapeutic efficacy in 123I- and 131I-MIBG in neuroblastoma
Catecholamines in Neuroblastoma
As clinical PI, a part of the care is in the clinic, treating patients with solid tumors and another part is translations research in the laboratory. One the one hand, clinical problems are easily spotted and on the other hand, laboratory findings are more easy translated to the clinic.
The major topics of the group are:
• The investigation of liquid biopsies in pediatric solid tumors focusses on the diagnostic use of bone marrow, peripheral blood for tumor diagnosis, staging and risk group allocation. The monitoring of response to therapy and early relapse detection are being performed in samples taken during treatment and follow-up. RNA-based qPCR, DNA qPCR, digital droplet PCR and NGS are performed in BM, blood and cell-free DNA and RNA. The major tumor types that are currently being studied are Neuroblastoma, Rhabdomyosarcoma and renal tumors. (PhD Lieke van Zogchel; Nathalie Lak)
• Diagnostic and therapeutic efficacy in 123I- and 131I-MIBG in neuroblastoma. After 30 years of experience in 131I-MIBG therapy for neuroblastoma and studying 123I-MIBG metastatic patterns, these studies are now integrated in a new project, in which in vitro MIBG uptake is being studied in different cell lines. Uptake, retention, expression of the different transporters are being studied in vitro, with the aim to translate this knowledge to the patients, to improve imaging for diagnosis and response measurement. (PhD Thomas Blom)
• Catecholamines in Neuroblastoma: a key hall mark ok neuroblastoma tumor is catecholamine metabolite production. Next to the 2 universal used markers (VMA & HVA), we have a panel of 8 markers, of which 3MT levels correlate with poor outcome. Biological and vitro studies are ongoing to elucidate the biological origin and effect of elevated 3MT levels. (PhD Iedan Verly)
To assess the clinical use of liquid biopsies we aim to study all body fluids. We use qPCR, NGS, ddPCR and collect plasma for cell free detection, tumor derived vesicles containing DNA and RNA.
Stutterheim J., Gerritsen A., Zappeij-Kannegieter L., Kleijn I., Dee R., Hooft L., van Noesel M., Bierings M., BertholdF., Versteeg R., Caron H.N., van der Schoot C.e., Tytgat G.A. PHOX2B is a novel and specific marker for minimal residual disease testing in neuroblastoma. (2008) J Clin Oncol. 26:5443-9. PubMed PMID: 18838715
Stutterheim J, Ichou FA, den Ouden E, Versteeg R, Caron HN, Tytgat GA, van der Schoot CE. Methylated RASSF1a is the first specific DNA marker for minimal residual disease testing in neuroblastoma. (2012) Clin Cancer Res. 18:808-14. PubMed PMID: 22142825
Bleeker G, van Eck-Smit BL, Zwinderman KH, Versteeg R, van Noesel MM, Kam BL, Kaspers GJ, van Schie A, Kreissman SG, Yanik G, Hero B, Schmidt M, Laureys G, Lambert B, Ora I, Schulte JH, Caron HN, Tytgat GA. MIBG scans in patients with stage 4 neuroblastoma reveal two metastatic patterns, one is associated with MYCN amplification and in MYCN-amplified tumours correlates with a better prognosis. (2014) Eur J Nucl Med Mol Imaging. 42:222-30. PubMed PMID: 25267348
van Wezel EM, Zwijnenburg D, Zappeij-Kannegieter L, Bus E, van Noesel MM, Molenaar JJ, Versteeg R, Fiocco M, Caron HN, van der Schoot CE, Koster J, Tytgat GA. Whole-genome sequencing identifies patient-specific DNA minimal residual disease markers in neuroblastoma. (2015) J Mol Diagn. 17:43-52. PubMed PMID: 25445214
Verly IRN, van Kuilenburg ABP, Abeling NGGM, Goorden SMI, Fiocco M, Vaz FM, van Noesel MM, Zwaan CM, Kaspers GJL, Merks JHM, Caron HN, Tytgat GAM. 3-Methoxytyramine: An independent prognostic biomarker that associates with high-risk disease and poor clinical outcome in neuroblastoma patients. (2018) Eur J Cancer. b102-110. PubMed PMID: 29274926
PI: Lieve Tytgat