Chordoma and chondrosarcoma gene profile: Implications for immunotherapy Journal Article


Authors: Schwab, J. H.; Boland, P. J.; Agaram, N. P.; Socci, N. D.; Guo, T.; O'toole, G. C.; Wang, X.; Ostroumov, E.; Hunter, C. J.; Block, J. A.; Doty, S.; Ferrone, S.; Healey, J. H.; Antonescu, C. R.
Article Title: Chordoma and chondrosarcoma gene profile: Implications for immunotherapy
Abstract: Chordoma and chondrosarcoma are malignant bone tumors characterized by the abundant production of extracellular matrix. The resistance of these tumors to conventional therapeutic modalities has prompted us to delineate the gene expression profile of these two tumor types, with the expectation to identify potential molecular therapeutic targets. Furthermore the transcriptional profile of chordomas and chrondrosarcomas was compared to a wide variety of sarcomas as well as to that of normal tissues of similar lineage, to determine whether they express unique gene signatures among other tumors of mesenchymal origin, and to identify changes associated with malignant transformation. A HG-U133A Affymetrix Chip platform was used to determine the gene expression signature in 6 chordoma and 14 chondrosarcoma lesions. Validation of selected genes was performed by qPCR and immunohistochemistry (IHC) on an extended subset of tumors. By unsupervised clustering, chordoma and chondrosarcoma tumors grouped together in a genomic cluster distinct from that of other sarcoma types. They shared overexpression of many extracellular matrix genes including aggrecan, type II & X collagen, fibronectin, matrillin 3, high molecular weight-melanoma associated antigen (HMW-MAA), matrix metalloproteinase MMP-9, and MMP-19. In contrast, T Brachyury and CD24 were selectively expressed in chordomas, as were Keratin 8,13,15,18 and 19. Chondrosarcomas are distinguished by high expression of type IX and XI collagen. Because of its potential usefulness as a target for immunotherapy, the expression of HMW-MAA was analyzed by IHC and was detected in 62% of chordomas and 48% of chondrosarcomas, respectively. Furthermore, western blotting analysis showed that HMW-MAA synthesized by chordoma cell lines has a structure similar to that of the antigen synthesized by melanoma cells. In conclusion, chordomas and chondrosarcomas share a similar gene expression profile of up-regulated extracellular matrix genes. HMW-MAA represents a potential useful target to apply immunotherapy to these tumors. © 2008 Springer-Verlag.
Keywords: immunohistochemistry; adult; clinical article; controlled study; aged; bone neoplasms; unclassified drug; gene cluster; human cell; flow cytometry; polymerase chain reaction; gene overexpression; gene expression; gene expression profiling; models, biological; gelatinase b; cell line, tumor; sarcoma; scleroprotein; extracellular matrix; gene expression regulation, neoplastic; antibodies, monoclonal; immunotherapy; reverse transcriptase polymerase chain reaction; microarray analysis; oligonucleotide array sequence analysis; tumor cell line; western blotting; collagen; melanoma cell; genomics; melanoma antigen; upregulation; cytokeratin 19; malignant transformation; cd24 antigen; chondrosarcoma; chordoma; mesenchyme; genetic selection; hmw-maa; aggrecan; collagen 11; collagen 9; collagen type 10; collagen type 2; cytokeratin 13; cytokeratin 15; cytokeratin 18; cytokeratin 8; fibronectin; high molecular weight melanoma associated antigen; matrilin 3; matrix metalloproteinase 19
Journal Title: Cancer Immunology, Immunotherapy
Volume: 58
Issue: 3
ISSN: 0340-7004
Publisher: Springer  
Date Published: 2009-03-01
Start Page: 339
End Page: 349
Language: English
DOI: 10.1007/s00262-008-0557-7
PUBMED: 18641983
PROVIDER: scopus
PMCID: PMC3426285
DOI/URL:
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: CIIMD" - "Source: Scopus"
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MSK Authors
  1. Joseph H Schwab
    13 Schwab
  2. Patrick J Boland
    160 Boland
  3. Narasimhan P Agaram
    190 Agaram
  4. Cristina R Antonescu
    895 Antonescu
  5. Nicholas D Socci
    266 Socci
  6. Tianhua Guo
    22 Guo
  7. John H Healey
    547 Healey