title: 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: Department of Pathology, Rizzoli Institute, Bologna, Italy. Electronic address: stefania.benini@ior.it.
authors: Stefania
authors: S
authors: Benini
authors: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors: Stefania
authors: S
authors: Cocchi
authors: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors: Gabriella
authors: G
authors: Gamberi
authors: Department of Experimental Oncology, Rizzoli Institute, Bologna, Italy.
authors: Giovanna
authors: G
authors: Magagnoli
authors: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors: Daniela
authors: D
authors: Vogel
authors: Department of Experimental Oncology, Rizzoli Institute, Bologna, Italy.
authors: Cristina
authors: C
authors: Ghinelli
authors: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors: Alberto
authors: A
authors: Righi
authors: Department of Experimental Oncology, Rizzoli Institute, Bologna, Italy.
authors: Piero
authors: P
authors: Picci
authors: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors: Marco
authors: M
authors: Alberghini
authors: Department of Pathology, Rizzoli Institute, Bologna, Italy.
authors: Marco
authors: M
authors: Gambarotti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002813:Chondrosarcoma / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D018204:Neoplasms, Connective and Soft Tissue / Q000175:diagnosis* / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics*; D014178:Translocation, Genetic; D033921:Vesicular Transport Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002148:Calmodulin-Binding Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D035381:TATA-Binding Protein Associated Factors; C500986:EWSR1 protein, human; C102041:TAF15 protein, human; C096163:TFG protein, human; D033921:Vesicular Transport Proteins; C073366:TCF12 protein, human