Abstract
BackgroundNeuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system. Half of all cases are defined high-risk with an overall survival less than 40% at 5 years from diagnosis. The lack of in vitro models able to recapitulate the intrinsic heterogeneity of primary NB tumours has hindered progress in understanding disease pathogenesis and therapy response.MethodsHere we describe the establishment of 6 patient-derived organoids (PDOs) from cells of NB tumour biopsies capable of self-organising in a structure resembling the tissue of origin.ResultsPDOs recapitulate the histological architecture typical of the NB tumour. Moreover, PDOs expressed NB specific markers such as neural cell adhesion molecules, NB84 antigen, synaptophysin (SYP), chromogranin A (CHGA) and neural cell adhesion molecule NCAM (CD56). Analyses of whole genome genotyping array revealed that PDOs maintained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Furthermore, the PDOs showed stemness features and retained cellular heterogeneity reflecting the high heterogeneity of NB tumours.ConclusionsWe were able to create a novel preclinical model for NB exhibiting self-renewal property and allowing to obtain a reservoir of NB patients’ biological material useful for the study of NB molecular pathogenesis and to test drugs for personalised treatments.
Highlights
Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system
To further characterise the proliferative feature of the patient-derived organoids (PDOs), we evaluated the expression of the cell cycle markers phospho-Histone H3 by immunohistochemistry (Additional file 3: Figure S1b)
To strengthen the findings on PDOs ability to organise themselves as parental tumours, we compared PDOs structure versus cells growing as spheres
Summary
Neuroblastoma (NB) is a paediatric tumour of the sympathetic nervous system. Half of all cases are defined high-risk with an overall survival less than 40% at 5 years from diagnosis. More than half of the children are diagnosed as a metastatic disease (stage M patients), usually involving the bone marrow and/or skeleton [3] These patients, classified high-risk (HR)-NB, do not respond to standard therapeutic regimens and relapse with an overall survival (OS) rate lower than 40% at 5 years [4], despite advances in treatment strategies [5]. We developed the first patient-derived organoids (PDOs) model of NB as representative preclinical in vitro tool able to recapitulate molecular and phenotypic landscape of the original NB tumour. Further studies are needed to assess the PDOs’ wherewithal for several applications To our knowledge, this is the first organoid model derived from NB primary cells and represents a physiological model exploitable for the screening of personalised effective drugs against NB
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