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Chordoma and chondrosarcoma gene profile: implications for immunotherapy
Joseph H Schwab1, Patrick J Boland, Narasimhan P Agaram
1Department of Surgery, Orthopedic Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
Cancer Immunology, Immunotherapy : CII
|July 22, 2008
Summary
Chordomas and chondrosarcomas, rare bone cancers, share gene expression profiles, particularly in extracellular matrix production. High molecular weight-melanoma associated antigen (HMW-MAA) is a promising target for immunotherapy in these tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Chordoma and chondrosarcoma are malignant bone tumors known for abundant extracellular matrix production.
- Their resistance to conventional therapies necessitates identifying novel molecular therapeutic targets.
Purpose of the Study:
- To delineate the gene expression profile of chordoma and chondrosarcoma.
- To identify unique gene signatures and molecular targets for these bone tumors.
- To compare their transcriptional profiles with other sarcomas and normal tissues.
Main Methods:
- Gene expression profiling using Affymetrix HG-U133A Chip in 6 chordomas and 14 chondrosarcomas.
- Validation of selected genes via quantitative PCR (qPCR) and immunohistochemistry (IHC).
- Unsupervised clustering to compare tumor groups.
Main Results:
- Chordoma and chondrosarcoma tumors clustered together, distinct from other sarcomas.
- Shared overexpression of extracellular matrix genes, including aggrecan, collagen types II & X, fibronectin, and MMP-9.
- Chordomas showed selective expression of T Brachyury, CD24, and specific keratins; chondrosarcomas overexpressed collagen types IX & XI.
- High molecular weight-melanoma associated antigen (HMW-MAA) detected in 62% of chordomas and 48% of chondrosarcomas via IHC.
Conclusions:
- Chordoma and chondrosarcoma exhibit a common gene expression profile characterized by upregulated extracellular matrix genes.
- High molecular weight-melanoma associated antigen (HMW-MAA) is a potential immunotherapy target for chordoma and chondrosarcoma.
- Understanding these gene signatures aids in identifying therapeutic strategies for these bone malignancies.
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