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Updated: Aug 24, 2026
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
Profiling and functional annotation of mRNA gene expression in pediatric rhabdomyosarcoma and Ewing's sarcoma
Claudia Baer1, Mattias Nees, Stephen Breit
1Deparment of Pediatric Oncology, Hematology and Immunology, University Children's Hospital, Heidelberg, Germany. claudia.baer@med.uni-heidelberg.de
Abstract:
Using Affymetrix oligonucleotide microarrays, we analyzed mRNA gene expression patterns of 12 primary pediatric rhabdomyosarcomas (RMS) and 11 Ewing's sarcomas (EWS), which belong to the small round blue cell tumors (SRBCTs). Diagnostic classification of these cancers is frequently complicated by the highly similar appearance in routine histology, and additional molecular markers could significantly improve tumor classification. A combination of three independent statistical approaches (t-test, SAM, k-nearest neighborhood analysis) resulted in 101 highly significant probe sets that clearly discriminate between EWS and RMS. We identified novel marker transcripts that have not been previously associated with either RMS or EWS yet, including CITED2, glypican 3 (GPC3), and cyclin D1 (CCND1). Expression levels for selected candidate genes were validated by quantitative real-time reverse-transcription PCR. Furthermore, to identify biologically meaningful trends, functional annotations were assigned to 946 genes differentially expressed between EWS and RMS (t-test). Genes involved in protein biosynthesis (n = 28) and complex assembly (n = 9), lipid metabolism (n = 23), energy generation (n = 22), and mRNA processing (n = 11) were expressed significantly higher in EWS. Thus, functional annotation of tumor-specific genes reveals detailed insights into tumor biology and differentiation-specific expression patterns and gives important clues related to the possible cellular origin of these pediatric tumors. Supplementary material for this article is available at the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.
Insights
This study identifies 101 gene expression markers to distinguish pediatric rhabdomyosarcoma (RMS) from Ewing
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Pediatric small round blue cell tumors (SRBCTs), including rhabdomyosarcoma (RMS) and Ewing's sarcoma (EWS), present diagnostic challenges due to histological similarities.
- Accurate classification of these tumors is crucial for effective treatment and prognosis.
- Molecular markers can significantly improve diagnostic accuracy beyond routine histology.
Purpose of the Study:
- To identify novel gene expression markers that can reliably differentiate between pediatric RMS and EWS.
- To gain insights into the underlying biology and potential cellular origins of these pediatric cancers through functional gene annotation.
Main Methods:
- Analysis of mRNA gene expression patterns using Affymetrix oligonucleotide microarrays in 12 primary RMS and 11 EWS samples.
- Application of three statistical approaches (t-test, SAM, k-nearest neighborhood analysis) to identify significant probe sets.
- Validation of selected candidate gene expression using quantitative real-time reverse-transcription PCR.
- Functional annotation of differentially expressed genes to understand biological trends.
Main Results:
- 101 highly significant probe sets were identified that clearly discriminate between EWS and RMS.
- Novel marker transcripts, including CITED2, glypican 3 (GPC3), and cyclin D1 (CCND1), were discovered.
- Genes involved in protein biosynthesis, lipid metabolism, energy generation, and mRNA processing were significantly upregulated in EWS.
- Functional annotation revealed distinct biological trends and differentiation-specific expression patterns.
Conclusions:
- Gene expression profiling provides a powerful tool for distinguishing between RMS and EWS.
- The identified molecular markers and functional insights contribute to a better understanding of SRBCT biology.
- These findings offer clues regarding the cellular origins of these pediatric tumors and may aid in future classification efforts.
