Abstract
Over 1.4 million transcript tags expressed in 20 different human medulloblastomas were counted using serial analysis of gene expression. Digital gene expression profiles in the medulloblastoma were compared to multiple regions of the normal human brain, revealing 30 transcripts with high expression in multiple tumors and little or no expression in the normal cerebellum and other adult and pediatric brain regions. Using independent medulloblastoma samples and normal tissue, real-time PCR verified eight of nine selected genes as candidate tumor-associated antigens. Differential protein expression for CD24, prolactin and Topo2A was further confirmed by immunohistochemical analysis using medulloblastoma and normal brain sections and a tissue microarray. The genes highly expressed in the medulloblastoma include PRAME, a cancer-testis antigen and potential targets for immunotherapy.
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Acknowledgements
Medulloblastoma samples were provided by the Duke Brain Tumor Bank and the Pediatric Oncology Group via the NIH Collaborative Human Tissue Network. We thank Jennifer Shoemaker for statistics consulting, Dr Roger McLendon (Duke University Medical Center) for expert histopathology, Drs Anita Lal, Robert Beaty, Brian Fee, Keith Killian and Janete Cerutti for providing SAGE data on normal tissues, Dennis W Rickman for expert immunohistochemistry assistance, and Dr Steven Jones, Jacquie Schein and members of the BCGSC sequencing team for expert technical assistance. Funding was provided by the Cancer Genome Anatomy Project (NCI contract S98-146), NCI Grant U01 CA88128 and the Pediatric Brain Tumor Foundation of the United States.
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Boon, K., Edwards, J., Siu, IM. et al. Comparison of medulloblastoma and normal neural transcriptomes identifies a restricted set of activated genes. Oncogene 22, 7687–7694 (2003). https://doi.org/10.1038/sj.onc.1207043
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DOI: https://doi.org/10.1038/sj.onc.1207043
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