Abstract

Neuroblastoma (NB) is a neuroectodermal embryonic cancer that originates from primordial neural crest cells, and amongst pediatric cancers with high mortality rates. NB is categorized into high-, intermediate-, and low-risk cases. A significant proportion of high-risk patients who achieve remission have a minimal residual disease (MRD) that causes relapse. Whilst there exists a myriad of advanced treatment options for NB, it is still characterized by a high relapse rate, resulting in a reduced chance of survival. Disialoganglioside (GD2) is a lipo-ganglioside containing a fatty acid derivative of sphingosine that is coupled to a monosaccharide and a sialic acid. Amongst pediatric solid tumors, NB tumor cells are known to express GD2; hence, it represents a unique antigen for subclinical NB MRD detection and analysis with implications in determining a response for treatment. This article discusses NB MRD expression and analytical assays for GD2 detection and quantification as well as computational approaches for GD2 characterization based on high-throughput image processing and genomic data analysis.

Highlights

  • NB is a solid tumor that originates from the primordial neural crest cells [1]

  • Age, histological category, grade of tumor differentiation, status of the MYCN oncogene, chromosome 11q status, and DNA ploidy, NB can be categorized as low, intermediate, or high-risk according to the International Neuroblastoma Risk Group (INRG) [3]

  • Current treatment methods used in High-risk NB (HRNB) maintain a combination of induction chemotherapy, local treatment by surgery and radiotherapy, consolidation with high-dose chemotherapy, and reinjection of autologous stem cell transplantation (ASCT), as well as maintenance therapy in residual disease using anti-GD2 monoclonal antibody (MoAB)-based treatments [5]

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Summary

Introduction

NB is a solid tumor that originates from the primordial neural crest cells [1] It is an extracranial tumor of the peripheral sympathetic nervous system that is typically found within the adrenal medulla. Current treatment methods used in HRNB maintain a combination of induction chemotherapy, local treatment by surgery and radiotherapy, consolidation with high-dose chemotherapy, and reinjection of autologous stem cell transplantation (ASCT), as well as maintenance therapy in residual disease using anti-GD2 monoclonal antibody (MoAB)-based treatments [5]. The main MRD detection methods applied to NB MRD are reverse transcriptase polymerase chain reaction (RT-PCR) that can detect one tumor cell in about 107 hematopoietic cells (HP), and immunocytological methods that can detect one tumor cell in about 105 HP cells The former utilizes the chemistry of disease-associated genetic biomolecules while the latter is based on disease-specific antigens. It discusses computational approaches that can be used for the characterization of NB and other neuroectodermal cancers based on high-throughput image processing of GD2 expression

Epidemiology of NB
Genomics of Neuroblastoma-GD2 Synthase Gene
Minimal Residual Disease in NB
GD2 Detection with Monoclonal Antibodies
GD2 Detection Using Aptamers
Immunohistolocal Image Processing Pipeline
Findings
Conclusions
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