The gene expression profile of extraskeletal myxoid chondrosarcoma

Subbaya Subramanian, Robert B. West, Robert J. Marinelli, Torsten O. Nielsen, Brian P. Rubin, John R. Goldblum, Rajiv M. Patel, Shirley Zhu, Kelli Montgomery, Tony L. Ng, Christopher L. Corless, Michael C. Heinrich, Matt van de Rijn

Research output: Contribution to journalReview article

49 Citations (Scopus)

Abstract

Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42 000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.

Original languageEnglish (US)
Pages (from-to)433-444
Number of pages12
JournalJournal of Pathology
Volume206
Issue number4
DOIs
StatePublished - Aug 1 2005

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Transcriptome
Sarcoma
Gene Expression Profiling
Neoplasms
Gene Expression
Microarray Analysis
Extraskeletal Myxoid Chondrosarcoma
Oligonucleotide Array Sequence Analysis
Lipid Metabolism
Genes
In Situ Hybridization
Histology
Therapeutics
Extremities
Carcinoma
Survival
Proteins

Keywords

  • Expressing profile
  • Extraskeletal myxoid chondrosarcoma
  • Lipid metabolism
  • Neuromedin B gene
  • Tissue microarray

Cite this

Subramanian, S., West, R. B., Marinelli, R. J., Nielsen, T. O., Rubin, B. P., Goldblum, J. R., ... van de Rijn, M. (2005). The gene expression profile of extraskeletal myxoid chondrosarcoma. Journal of Pathology, 206(4), 433-444. https://doi.org/10.1002/path.1792

The gene expression profile of extraskeletal myxoid chondrosarcoma. / Subramanian, Subbaya; West, Robert B.; Marinelli, Robert J.; Nielsen, Torsten O.; Rubin, Brian P.; Goldblum, John R.; Patel, Rajiv M.; Zhu, Shirley; Montgomery, Kelli; Ng, Tony L.; Corless, Christopher L.; Heinrich, Michael C.; van de Rijn, Matt.

In: Journal of Pathology, Vol. 206, No. 4, 01.08.2005, p. 433-444.

Research output: Contribution to journalReview article

Subramanian, S, West, RB, Marinelli, RJ, Nielsen, TO, Rubin, BP, Goldblum, JR, Patel, RM, Zhu, S, Montgomery, K, Ng, TL, Corless, CL, Heinrich, MC & van de Rijn, M 2005, 'The gene expression profile of extraskeletal myxoid chondrosarcoma', Journal of Pathology, vol. 206, no. 4, pp. 433-444. https://doi.org/10.1002/path.1792
Subramanian S, West RB, Marinelli RJ, Nielsen TO, Rubin BP, Goldblum JR et al. The gene expression profile of extraskeletal myxoid chondrosarcoma. Journal of Pathology. 2005 Aug 1;206(4):433-444. https://doi.org/10.1002/path.1792
Subramanian, Subbaya ; West, Robert B. ; Marinelli, Robert J. ; Nielsen, Torsten O. ; Rubin, Brian P. ; Goldblum, John R. ; Patel, Rajiv M. ; Zhu, Shirley ; Montgomery, Kelli ; Ng, Tony L. ; Corless, Christopher L. ; Heinrich, Michael C. ; van de Rijn, Matt. / The gene expression profile of extraskeletal myxoid chondrosarcoma. In: Journal of Pathology. 2005 ; Vol. 206, No. 4. pp. 433-444.
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abstract = "Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42 000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25{\%} likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.",
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AU - Rubin, Brian P.

AU - Goldblum, John R.

AU - Patel, Rajiv M.

AU - Zhu, Shirley

AU - Montgomery, Kelli

AU - Ng, Tony L.

AU - Corless, Christopher L.

AU - Heinrich, Michael C.

AU - van de Rijn, Matt

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N2 - Extraskeletal myxoid chondrosarcoma (EMC) is a soft tissue tumour that occurs primarily in the extremities and is characterized by a balanced translocation most commonly involving t(9;22) (q22;q12). The morphological spectrum of EMC is broad and thus a diagnosis based on histology alone can be difficult. Currently, no systemic therapy exists that improves survival in patients with EMC. In the present study, gene expression profiling has been performed to discover new diagnostic markers and potential therapeutic targets for this tumour type. Global gene expression profiling of ten EMCs and 26 other sarcomas using 42 000 spot cDNA microarrays revealed that the cases of EMC were closely related to each other and distinct from the other tumours profiled. Significance analysis of microarrays (SAM) identified 86 genes that distinguished EMC from the other sarcomas with 0.25% likelihood of false significance. NMB, DKK1, DNER, CLCN3, and DEF6 were the top five genes in this analysis. In situ hybridization for NMB gene expression on tissue microarrays (TMAs) containing a total of 1164 specimens representing 62 different sarcoma types and 15 different carcinoma types showed that was highly expressed in 17 of 22 EMC cases and very rarely expressed in other tumours and thus could function as a novel diagnostic marker. High levels of expression of PPARG and the gene encoding its interacting protein, PPARGC1A, in most EMCs suggest activation of lipid metabolism pathways in this tumour. Small molecule inhibitors for PPARG exist and PPARG could be a potential therapeutic target for EMC.

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