Diagnostic utility of molecular investigation in extraskeletal myxoid chondrosarcoma.

Abstract

Extraskeletal myxoid chondrosarcoma is characterized by the reciprocal chromosomal translocation t(9;22) and the resultant fused gene EWS RNA-binding protein 1 and nuclear receptor subfamily 4, group A, member 3 (EWSR1-NR4A3). A second cytogenetic rearrangement t(9;17) involves the genes NR4A3 and TAF 15 RNA polymerase II, TATA box binding protein (TBP)-associated factor (TAF15). Less frequent fusion transcript variants of the NR4A3 gene, transcription factor 12 (TCF12)-NR4A3 and TRK-fused gene (TFG)-NR4A3, are associated with t(9;15) and t(9;3) respectively. The samples from 42 patients with extraskeletal myxoid chondrosarcoma were examined for the presence of EWSR1-NR4A3, TAF15-NR4A3, TCF12-NR4A3, and TFG-NR4A3 fusion transcripts by using RT-PCR. Fluorescence in situ hybridization was performed to analyze the status of EWSR1 and NR4A3 genes. The fusion transcripts were detected in 34 of 42 samples (81%); the presence of an EWSR1 or NR4A3 gene rearrangements were detected in 8 of 42 samples (19%) which had tested negative for all fusion transcripts detected by RT-PCR. Of the 34 samples evaluable for fusion transcripts, 23 yielded positive results for EWSR1-NR4A3, 10 for TAF15-NR4A3, and 1 for TCF12-NR4A3. The combination of RT-PCR and fluorescence in situ hybridization on frozen and paraffin-embedded tissue is a sensitive and specific method for molecular detection of recurrent translocations and is an important ancillary method to establish the diagnosis of extraskeletal myxoid chondrosarcoma.

• Authors: Stefania Benini, Stefania Cocchi, Gabriella Gamberi, Giovanna Magagnoli, Daniela Vogel, Cristina Ghinelli, Alberto Righi, Piero Picci, Marco Alberghini, Marco Gambarotti
• Journal: The Journal of molecular diagnostics : JMD (J Mol Diagn) Vol. 16 Issue 3 Pg. 314-23 (May 2014) ISSN: 1943-7811 [Electronic] United States
• PMID: 24508382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Calmodulin-Binding Proteins
• EWSR1 protein, human
• Oncogene Proteins, Fusion
• Proteins
• RNA-Binding Protein EWS
• RNA-Binding Proteins
• TAF15 protein, human
• TATA-Binding Protein Associated Factors
• TFG protein, human
• TCF12 protein, human

Topics

• Adult
• Aged
• Aged, 80 and over
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• Calmodulin-Binding Proteins (genetics)
• Chondrosarcoma (diagnosis, genetics)
• Female
• Gene Rearrangement
• Humans
• In Situ Hybridization, Fluorescence
• Male
• Middle Aged
• Neoplasms, Connective and Soft Tissue (diagnosis, genetics)
• Oncogene Proteins, Fusion (genetics)
• Proteins (genetics)
• RNA-Binding Protein EWS
• RNA-Binding Proteins (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• TATA-Binding Protein Associated Factors (genetics)
• Translocation, Genetic