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Gene profiling of high risk neuroblastoma
Sanjeev A Vasudevan1, Jed G Nuchtern, Jason M Shohet
1Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 6621 Fannin, CC 650.00, Houston, Texas 77030, USA.
Insights
High-risk neuroblastoma in children presents challenges, but identifying prognostic markers like MYCN amplification and gene expression is key. Research focuses on understanding these molecular features to improve patient outcomes.
Area of Science:
- Pediatric Oncology
- Molecular Genetics
- Cancer Biology
Background:
- Neuroblastoma is a common childhood cancer with variable presentation and outcomes.
- High-risk neuroblastoma has a poor prognosis, with survival rates around 30% for aggressive or metastatic cases.
Purpose of the Study:
- To review prognostically significant histologic and molecular features of high-risk neuroblastoma.
- To propose an algorithm for dissecting differentially expressed genes that define high-risk neuroblastoma phenotypes.
- To highlight the utility of expression microarrays in profiling advanced-stage neuroblastoma.
Main Methods:
- Review of established prognostic indicators including age, stage, histopathology, ploidy, and MYCN oncogene amplification.
- Analysis of other potential markers such as chromosome 1p deletion, 17q gain, receptor tyrosine kinases (trk-A, trk-B), CD44, CXCR4, and multidrug resistance associated protein (MRP).
- Utilizing expression microarrays to profile advanced-stage neuroblastoma and identify differentially expressed genes.
Main Results:
- Established markers (age, stage, histopathology, ploidy, MYCN amplification) correlate well with neuroblastoma outcomes.
- Identified genes related to cell cycle control, DNA/RNA replication, ribosomal synthesis, neuronal differentiation, and signal transduction.
- Demonstrated the utility of analyzing specific gene targets, such as the MYCN transcription factor and its target gene MCM7.
Conclusions:
- Accurate prognostication of neuroblastoma relies on a combination of clinical, histologic, and molecular markers.
- Differential gene expression analysis using microarrays offers a powerful approach to understand the molecular basis of high-risk neuroblastoma.
- Further research into specific gene targets like MYCN and MCM7 can refine risk stratification and potentially guide therapeutic strategies.
Abstract:
Neuroblastoma, a cancer of young children, is well known for its diverse pattern of presentation. Approximately one-half of children have localized tumors that can be cured with surgery alone. The remaining children have widespread metastatic disease or quite large, aggressive, localized tumors. These children have a poor long-term survival rate of approximately 30%. We review the prognostically significant histologic and molecular features of high risk neuroblastoma and propose an algorithm to dissect further the differentially expressed genes that define the phenotype of this disease. Over the past 25 years, much effort has gone into establishing reliable prognostic indicators of high risk disease. For neuroblastoma, age, stage, and histopathology have time and again correlated well with outcomes. Chromosomal number, or ploidy, and amplification of the MYCN oncogene have proved to be equally as important and are commonly used to stratify patient risk. Other potentially lucrative markers include chromosome 1p deletion, chromosome 17q gain, receptor tyrosine kinases A and B (trk-A, trk-B), CD44, CXCR4, and multidrug resistance associated protein (MRP). With the onset of new technology, expression microarrays are now being used to profile advanced-stage neuroblastoma on a larger scale. Genes particular to cell cycle control, DNA/RNA replication, ribosomal synthesis, neuronal differentiation, and intracellular/extracellular signal transduction have been identified through differential expression analysis. We present our research on the MYCN transcription factor and target gene, MCM7, to show the utility of this approach.