European association involved in the research and care of children with neuroblastoma - SIOPEN

Aims

The SIOPEN Molecular Monitoring Group collaborates to develop and validate high-precision minimally invasive methods to objectively assess disease status and patient response, with the goal of improving outcomes for children with neuroblastoma.

Since the bone marrow is a common site of metastasis and relapse, our research has focused on biomarkers in the bone marrow, peripheral blood stem cells and blood.

The description and validation of clinically informative biomarkers in blood is particularly attractive, as this could provide a minimally invasive test for prognostication and monitoring of children throughout the disease course. This is exemplified by outputs of our prospective quality controlled study, examining the prognostic and predictive value of the adrenergic neuroblastoma mRNAs tyrosine hydroxylase and paired-like homeobox 2B mRNAs in blood and bone marrow from children with neuroblastoma entered into HR-NBL-1/SIOPEN1-4. We are also investigating the role of small RNAs including microRNAs, which may be important for prognostication and might also identify new targets for the development of novel therapeutics to eradicate metastatic drug resistant disease. In a proof of concept study microRNAs in plasma-derived exosomes have been shown to predict response to induction-chemotherapy and may be markers of sensitivity to specific drugs.

• To ensure the quality of our studies the SIOPEN MMG establish standard operating procedures for sample collection, transport, storage and analyses.

• We maintain quality assurance within the SIOPEN MMG reference laboratories through biannual blinded quality control studies.

We are grateful to our collaborators who help with study design, data analyses and interpretation, including Dr Ulli Pötschger (Austria), Professor Walter Gregory (United Kingdom), Ms Aimee Houlton (United Kingdom), Dr Stefano Parodi (Italy), Professor Keith Wheatley (United Kingdom), national coordinators, Professor Dominique Valteau-Couanet and Professor Ruth Ladenstein.

 

Selected outputs

1 Viprey VF, Corrias MV, Kagedal B, Oltra S, Swerts K, Vicha A, Ladenstein R, Burchill SA. Standardisation of operating procedures for the detection of minimal disease by QRT-PCR in children with neuroblastoma: quality assurance on behalf of SIOPEN-R-NET. European Journal of Cancer, 43(2), 341-350, 2007

2 Viprey V, Lastowska M, Corrias M, Swerts K, Jackson M, Burchill S. Minimal disease monitoring by QRT-PCR: Guidelines for identification and systematic validation of molecular markers prior to evaluation in prospective clinical trials. The Journal of Pathology, 216(2), 245-252, 2008.

3 Viprey VF, Gregory WM, Corrias MV, Tchirkov A, Swerts K, Vicha A, Dallorso S, Brock P, Luksch R, Valteau-Couanet D, Papadakis V, Laureys G, Ladenstein R and Burchill SA. Detection of mRNA in bone marrow and blood by RT-qPCR predicts event-free and overall survival in children with stage 4 neuroblastoma at diagnosis; a SIOPEN Molecular Monitoring Group study. Journal of Clinical Oncology, 32; 1074-83, 2014.

4 Corrias M, Paordi S, Tchirkov A, Lammens T, Vicha A, Pasqualini C, Trager C, Yanez Y, Dallorso S, Varesio L, Luksch R, Laureys G, Valteau-Couanet D, Canete A, Poetschger U, Ladenstein R, Burchill SA. Event-free survival of infants and toddlers enrolled in the HR-NBL-1/SIOPEN trial is associated with the level of neuroblastoma mRNAs at diagnosis. Pediatr Blood Cancer. 65(7):e27052, 2018.

5 Morini M, Cangelosi D, Segalerba D, Marimpietri D, Raggi F, Castellano A, Fruci D, de Mora JF, Cañete A, Yáñez Y, Viprey V, Corrias MV, Carlini B, Pezzolo A, Schleiermacher G, Mazzocco K, Ladenstein R , Sementa AR, Conte M, Garaventa A, Burchill S, Luksch R, Bosco MC, Eva A, Varesio L. Exosomal microRNAs from Longitudinal Liquid Biopsies for the Prediction of Response to Induction Chemotherapy in High-Risk Neuroblastoma Patients: A Proof of Concept SIOPEN Study. Cancers (Basel). 11, 1476, 2019