Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma

Rachel I. Brody, Takafumi Ueda, Aimée Hamelin, Suresh C. Jhanwar, Julia A. Bridge, John H. Healey, Andrew G. Huvos, William L. Gerald, Marc Ladanyi

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Abstract

The pathogenesis of myxoid chondrosarcoma (CS) is poorly understood. A recurrent translocation, t(9;22)(q22;q12), has been recognized in CS, specifically in extraskeletal myxoid CS. Recently, this translocation has been shown to represent a rearrangement of the EWS gene at 22q12 with a novel gene at 9q22 designated CHN (or TEC). Sequence analysis suggests that CHN encodes a novel orphan nuclear receptor with a zinc finger DNA-binding domain. The structure of this gene fusion has been characterized in only a limited number of extraskeletal myxoid CSs and its presence in other types of CS has not been extensively examined. We studied 46 cases of CS (8 extraskeletal myxoid, 4 skeletal myxoid, 4 mesenchymal, and 30 other) for the EWS/CHN gene fusion by reverse transcriptase polymerase chain reaction. Southern blotting, and long-range DNA polymerase chain reaction. The EWS/CHN gene fusion was present in 6 of 8 extraskeletal myxoid CSs and was not detected in any of the remaining cases, including the 4 skeletal myxoid CSs. The negative findings in the latter cases suggest that skeletal myxoid CS is pathogenetically distinct from its extraskeletal counterpart. Notably, 2 cases of extraskeletal myxoid CS showed neither an EWS/CHN fusion transcript nor EWS/CHN genomic fusion nor EWS or CHN genomic rearrangement, suggesting genetic heterogeneity within extraskeletal myxoid CS. Finally, we also provide evidence for alternative splicing of the 3' end of the fusion transcript. Extraskeletal myxoid CS thus represents yet another sarcoma type containing a gene fusion involving EWS.

Original languageEnglish (US)
Pages (from-to)1049-1058
Number of pages10
JournalAmerican Journal of Pathology
Volume150
Issue number3
StatePublished - Mar 17 1997

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Orphan Nuclear Receptors
Chondrosarcoma
Gene Fusion
Genes
Genetic Heterogeneity
Gene Rearrangement
Zinc Fingers
Alternative Splicing
DNA-Directed DNA Polymerase
Southern Blotting
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma
Sequence Analysis
Extraskeletal Myxoid Chondrosarcoma
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Brody, R. I., Ueda, T., Hamelin, A., Jhanwar, S. C., Bridge, J. A., Healey, J. H., ... Ladanyi, M. (1997). Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. American Journal of Pathology, 150(3), 1049-1058.

Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. / Brody, Rachel I.; Ueda, Takafumi; Hamelin, Aimée; Jhanwar, Suresh C.; Bridge, Julia A.; Healey, John H.; Huvos, Andrew G.; Gerald, William L.; Ladanyi, Marc.

In: American Journal of Pathology, Vol. 150, No. 3, 17.03.1997, p. 1049-1058.

Research output: Contribution to journalArticle

Brody, RI, Ueda, T, Hamelin, A, Jhanwar, SC, Bridge, JA, Healey, JH, Huvos, AG, Gerald, WL & Ladanyi, M 1997, 'Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma', American Journal of Pathology, vol. 150, no. 3, pp. 1049-1058.
Brody RI, Ueda T, Hamelin A, Jhanwar SC, Bridge JA, Healey JH et al. Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. American Journal of Pathology. 1997 Mar 17;150(3):1049-1058.
Brody, Rachel I. ; Ueda, Takafumi ; Hamelin, Aimée ; Jhanwar, Suresh C. ; Bridge, Julia A. ; Healey, John H. ; Huvos, Andrew G. ; Gerald, William L. ; Ladanyi, Marc. / Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. In: American Journal of Pathology. 1997 ; Vol. 150, No. 3. pp. 1049-1058.
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